Brief Summary
This trial studies how well paclitaxel, trastuzumab, and pertuzumab work in eliminating further chemotherapy after surgery in patients with HER2-positive stage II-IIIa breast cancer who have no cancer remaining at surgery (either in the breast or underarm lymph nodes) after pre-operative chemotherapy and HER2-targeted therapy. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab and pertuzumab are both a form of "targeted therapy" because they work by attaching themselves to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When these drugs attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving paclitaxel, trastuzumab, and pertuzumab may enable fewer chemotherapy drugs to be given without compromising patient outcomes compared to the usual treatment.
Brief Title
CompassHER2-pCR: Decreasing Chemotherapy for Breast Cancer Patients After Pre-surgery Chemo and Targeted Therapy
Detailed Description
PRIMARY OBJECTIVES:
I. To determine if 3-year recurrence-free survival (RFS) is greater than 92% among clinical stages II or IIIa patients with HER2-positive breast cancer who achieve pathologic complete response (pCR) (ypT0/is ypN0) after preoperative therapy with 12 weeks of a taxane, trastuzumab (or Food and Drug Administration \[FDA\] approved biosimilar) and pertuzumab (THP x 12).
SECONDARY OBJECTIVES:
I. To determine 3-year IDFS (invasive disease-free survival), DDFS (distant disease-free survival), DRFS (distant relapse-free survival), RFI (recurrence-free interval), OS (overall survival) and breast cancer-specific survival in patients who achieve pCR (and by pretreatment clinical stage). (Secondary Clinical Objective) II. To determine 3-year EFS (event-free survival) in all patients from time of study registration. (Secondary Clinical Objective) III. To evaluate safety and tolerability for all patients during the pre-operative phase and for patients who attain pCR and de-escalate therapy (Arm A) until the completion of post-surgery protocol assigned therapy (i.e. until the end of trastuzumab and pertuzumab \[HP\] therapy). (Secondary Clinical Objective) IV. To evaluate the association of estrogen receptor (ER) status in the untreated primary tumor with pathologic response and with long-term survival outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS, and breast cancer-specific survival). (Secondary Correlative Objective) V. To evaluate the associations of detection of circulating tumor cells (CTCs) in the blood at baseline with pCR. (Secondary Correlative Objective) VI. To evaluate the association of detection of CTCs in the blood at baseline, after 3 weeks of THP, after 12 weeks of THP (before surgery), after surgery before any additional therapy, and after completion of HER2-targeted therapy with RFS in patients who achieve pCR or not. (Secondary Correlative Objective)
EXPLORATORY OBJECTIVES:
I. To determine 3-year RFS, IDFS (invasive disease-free survival), DDFS (distant disease-free survival), DRFS (distant relapse-free survival), RFI (recurrence-free interval), OS (overall survival) and breast cancer-specific survival in patients who do not achieve pCR (and by pretreatment clinical stage). (Exploratory Clinical Objective) II. To determine the pathologic response to THP neoadjuvant therapy, as assessed by residual cancer burden (RCB). (Exploratory Clinical Objective) III. To determine the association between residual cancer burden (RCB) and all described standardized definitions for efficacy end points (STEEP) criteria outcomes. (Exploratory Clinical Objective) IV. To determine the false negative rate (FNR) of limited staging procedures (defined as sentinel lymph node biopsy \[SLNB\] plus removal of clipped node) in patients who undergo such procedures with a planned axillary lymph node dissection (ALND). (Exploratory Clinical Objective) V. To determine axillary pCR rates as a function of the burden of disease at presentation as determined on pre-treatment ultrasound (US) and the axillary staging technique (SLNB plus ensuring removal of clipped node versus ALND). (Exploratory Clinical Objective) VI. To evaluate the associations between plasma tumor cell-free deoxyribonucleic acid (DNA) (cfDNA) tumor-specific mutations (baseline and after therapy) with pathologic response and long-term outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS, and breast cancer-specific survival). (Exploratory Correlative Objective) VII. To evaluate the associations between tumor infiltrating lymphocytes (TILs) and immune activation gene signatures in the baseline tumor with pathologic response and long-term outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS and breast cancer-specific survival). (Exploratory Correlative Objective) VIII. To determine the frequency of change in intrinsic subtype between pretreatment tumor specimen and residual disease at the time of surgery. (Exploratory Correlative Objective) IX. To evaluate the associations between DNA copy number, DNA mutations, ribonucleic acid (RNA) expression and protein expression in the baseline tumor and changes from baseline to post-THP therapy with pathologic response and long-term outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS, and breast cancer-specific survival). (Exploratory Correlative Objective)
OUTLINE:
PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxel intravenously (IV) on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of the treating oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard of care lumpectomy and/or mastectomy.
POST-OPERATIVE/ADJUVANT THERAPY: Patients are assigned to 1 of 2 arms.
ARM A: Patients with pCR after surgery receive trastuzumab and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy and receive hormone therapy if appropriate.
ARM B: Patients with remaining tumor after surgery receive standard of care trastuzumab emtansine for 14 doses in the absence of disease progression or unacceptable toxicity. Patients may also receive additional standard of care chemotherapy, as well as hormone therapy if appropriate.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2-5 years, then annually for 5-15 years from date of surgery.
I. To determine if 3-year recurrence-free survival (RFS) is greater than 92% among clinical stages II or IIIa patients with HER2-positive breast cancer who achieve pathologic complete response (pCR) (ypT0/is ypN0) after preoperative therapy with 12 weeks of a taxane, trastuzumab (or Food and Drug Administration \[FDA\] approved biosimilar) and pertuzumab (THP x 12).
SECONDARY OBJECTIVES:
I. To determine 3-year IDFS (invasive disease-free survival), DDFS (distant disease-free survival), DRFS (distant relapse-free survival), RFI (recurrence-free interval), OS (overall survival) and breast cancer-specific survival in patients who achieve pCR (and by pretreatment clinical stage). (Secondary Clinical Objective) II. To determine 3-year EFS (event-free survival) in all patients from time of study registration. (Secondary Clinical Objective) III. To evaluate safety and tolerability for all patients during the pre-operative phase and for patients who attain pCR and de-escalate therapy (Arm A) until the completion of post-surgery protocol assigned therapy (i.e. until the end of trastuzumab and pertuzumab \[HP\] therapy). (Secondary Clinical Objective) IV. To evaluate the association of estrogen receptor (ER) status in the untreated primary tumor with pathologic response and with long-term survival outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS, and breast cancer-specific survival). (Secondary Correlative Objective) V. To evaluate the associations of detection of circulating tumor cells (CTCs) in the blood at baseline with pCR. (Secondary Correlative Objective) VI. To evaluate the association of detection of CTCs in the blood at baseline, after 3 weeks of THP, after 12 weeks of THP (before surgery), after surgery before any additional therapy, and after completion of HER2-targeted therapy with RFS in patients who achieve pCR or not. (Secondary Correlative Objective)
EXPLORATORY OBJECTIVES:
I. To determine 3-year RFS, IDFS (invasive disease-free survival), DDFS (distant disease-free survival), DRFS (distant relapse-free survival), RFI (recurrence-free interval), OS (overall survival) and breast cancer-specific survival in patients who do not achieve pCR (and by pretreatment clinical stage). (Exploratory Clinical Objective) II. To determine the pathologic response to THP neoadjuvant therapy, as assessed by residual cancer burden (RCB). (Exploratory Clinical Objective) III. To determine the association between residual cancer burden (RCB) and all described standardized definitions for efficacy end points (STEEP) criteria outcomes. (Exploratory Clinical Objective) IV. To determine the false negative rate (FNR) of limited staging procedures (defined as sentinel lymph node biopsy \[SLNB\] plus removal of clipped node) in patients who undergo such procedures with a planned axillary lymph node dissection (ALND). (Exploratory Clinical Objective) V. To determine axillary pCR rates as a function of the burden of disease at presentation as determined on pre-treatment ultrasound (US) and the axillary staging technique (SLNB plus ensuring removal of clipped node versus ALND). (Exploratory Clinical Objective) VI. To evaluate the associations between plasma tumor cell-free deoxyribonucleic acid (DNA) (cfDNA) tumor-specific mutations (baseline and after therapy) with pathologic response and long-term outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS, and breast cancer-specific survival). (Exploratory Correlative Objective) VII. To evaluate the associations between tumor infiltrating lymphocytes (TILs) and immune activation gene signatures in the baseline tumor with pathologic response and long-term outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS and breast cancer-specific survival). (Exploratory Correlative Objective) VIII. To determine the frequency of change in intrinsic subtype between pretreatment tumor specimen and residual disease at the time of surgery. (Exploratory Correlative Objective) IX. To evaluate the associations between DNA copy number, DNA mutations, ribonucleic acid (RNA) expression and protein expression in the baseline tumor and changes from baseline to post-THP therapy with pathologic response and long-term outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS, and breast cancer-specific survival). (Exploratory Correlative Objective)
OUTLINE:
PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxel intravenously (IV) on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of the treating oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard of care lumpectomy and/or mastectomy.
POST-OPERATIVE/ADJUVANT THERAPY: Patients are assigned to 1 of 2 arms.
ARM A: Patients with pCR after surgery receive trastuzumab and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy and receive hormone therapy if appropriate.
ARM B: Patients with remaining tumor after surgery receive standard of care trastuzumab emtansine for 14 doses in the absence of disease progression or unacceptable toxicity. Patients may also receive additional standard of care chemotherapy, as well as hormone therapy if appropriate.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2-5 years, then annually for 5-15 years from date of surgery.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Anatomic Stage II Breast Cancer AJCC v8
Anatomic Stage IIA Breast Cancer AJCC v8
Anatomic Stage IIB Breast Cancer AJCC v8
Anatomic Stage IIIA Breast Cancer AJCC v8
Invasive Breast Carcinoma
Prognostic Stage II Breast Cancer AJCC v8
Prognostic Stage IIA Breast Cancer AJCC v8
Prognostic Stage IIB Breast Cancer AJCC v8
Prognostic Stage IIIA Breast Cancer AJCC v8
Eligibility Criteria
Inclusion Criteria:
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Patient must have histologically confirmed HER2-positive primary invasive breast carcinoma, determined by local testing. The tumor must have either HER2 IHC result of 3+ or HER2/CEP17 ratio \> 2 with \> 4.0 HER2 signals per cell by ISH. Tumors with HER2/CEP17 ISH ratio \< 2 are ineligible, even if HER2 copy number is \> 6, unless HER2 IHC result is 3+.
* Patients hormone receptor (estrogen receptor \[ER\] and progesterone receptor \[PR\]) status must be known and will be determined by local testing. Patients with either hormone receptor -positive or hormone receptor- negative HER2-positive breast cancer are eligible
* Patients must have AJCC 8th Edition stage II or IIIa according to anatomic staging table at diagnosis
* Patients without nodal involvement (cN0) are eligible if T size \> 2.0 cm (T2-3)
* Patients with nodal involvement (cN1-2) are eligible if T1-3
* Patients with clinical T4 or N3 disease are not eligible
* Patient must be willing and able (i.e., have no contraindication) to receive standard adjuvant therapy, consisting of HER2-directed therapy, radiation (if indicated) and endocrine therapy (if ER+) if achieving pCR at surgery
* Patient with bilateral invasive breast cancers are eligible if both cancers are HER2-positive (as defined in 3.1.3) at least one meets protocol eligibility and neither cancer renders the patient ineligible (i.e. per eligibility 3.1.5)
* Patients with multiple ipsilateral invasive tumors are eligible as long as all tumors are HER2-positive, and at least one tumor focus meets eligibility criteria (per eligibility 3.1.5). Multiple lesions that appear part of the same index tumor do not require additional biopsy/HER2 testing. Multiple lesions that appear part of the same index tumor do not require additional biopsy/HER2 testing. However, even if biopsy is not deemed necessary, consideration should be given to placing a clip in any lesion that is 1 cm or further from the primary tumor to ensure that all tumor is removed at surgery AND that the pathologist can locate all primary sites of tumor to assess pathologic response at surgery.
* Patients with a history of other non-breast malignancies are eligible if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
* Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, and localized papillary or follicular thyroid cancer who have completed recommended treatment including surgery. Patients with any other cancers within the last 5 years are ineligible.
* Patents must have a left ventricular ejection fraction (LVEF) within normal institutional parameters (or \> 50%)
* Patients must not have \> grade 1 peripheral neuropathy of any etiology.
* Patients must have a bilateral mammogram and a diagnostic breast ultrasound \[on the side of the cancer(s)\] (with or without breast MRI) performed at screening. An axillary ultrasound on the side of the cancer(s) is also required. However, if a patient has a negative axillary physical exam and a baseline MRI without suspicious lymph nodes performed before axillary ultrasound, axillary ultrasound may be omitted. Comprehensive breast and axillary imaging must be performed within 42 days of registration (i.e. the patient's mammogram/ breast ultrasound /axillary ultrasound OR their breast MRI).
* Baseline imaging of the ipsilateral axilla by ultrasound or breast MRI is mandatory. For subjects with axillary lymph node(s) suspicious on clinical exam or imaging, patient must be willing to have a needle aspiration or core biopsy to determine the presence of metastatic disease in the lymph nodes. A clip must be placed in the involved axillary lymph node. (If there are more than 1 suspicious axillary nodes, only one clipped node is required).
* Patient of childbearing potential and sexually active patients must use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for 7 months after the last dose of study treatment.
* Patient must be willing and able to sign informed consent
* Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to protocol registration)
* Absolute neutrophil count \>= 1,500/mcL (obtained =\< 28 days prior to protocol registration)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to protocol registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (obtained =\< 28 days prior to protocol registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 28 days prior to protocol registration)
* Creatinine =\< 1.5 x institutional ULN (obtained =\< 28 days prior to protocol registration)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Exclusion Criteria:
* Patients must not have impaired decision-making capacity
* Patient must not have a history of any prior (ipsilateral or contralateral) invasive breast cancer
* One exception: a patient with a history of T1N0 triple negative breast cancer diagnosed more than 10 years earlier, who remains disease free is eligible
* Patient must not have prior ipsilateral ductal breast carcinoma in situ (DCIS). Patients with prior lobular breast carcinoma in situ (LCIS), atypical hyperplasia, other high risk benign lesions or contralateral DCIS (without evidence of microinvasion) are eligible
* NOTE: Patients currently receiving endocrine therapy for prior contralateral DCIS are eligible
* Patient must not have stage IV (metastatic) breast cancer
* Staging studies (computed tomography \[CT\] chest/abdomen/pelvis and a bone scan or positron emission tomography \[PET\]-CT scan) are required for stage III disease or those with abnormal baseline liver function tests (LFTs), symptoms (e.g. new bone pain) or abnormal physical exam findings (National Comprehensive Cancer Network \[NCCN\] guidelines version \[V\]1.2019)
* Patient must not have T4 and/or N3 disease, including inflammatory breast cancer
* Patient must not have any prior treatment for the current breast cancer, including surgery, chemotherapy, hormonal therapy, radiation or experimental therapy
* Patients must not have \> grade 1 peripheral neuropathy of any etiology
* Patient must not have a concurrent serious medical condition that would preclude completion of study therapy. For example, uncontrolled hypertension (systolic \> 180 mm Hg and/or diastolic \> 100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to registration, unstable angina, congestive heart failure (CHF) or serious cardiac arrhythmia requiring medication and other concurrent serious diseases that may interfere with planned treatment
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. Patients must also not expect to conceive from the time of registration, while on study treatment, and until at least 7 months after the last dose of study treatment. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
* All patients of childbearing potential is anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Patient must have histologically confirmed HER2-positive primary invasive breast carcinoma, determined by local testing. The tumor must have either HER2 IHC result of 3+ or HER2/CEP17 ratio \> 2 with \> 4.0 HER2 signals per cell by ISH. Tumors with HER2/CEP17 ISH ratio \< 2 are ineligible, even if HER2 copy number is \> 6, unless HER2 IHC result is 3+.
* Patients hormone receptor (estrogen receptor \[ER\] and progesterone receptor \[PR\]) status must be known and will be determined by local testing. Patients with either hormone receptor -positive or hormone receptor- negative HER2-positive breast cancer are eligible
* Patients must have AJCC 8th Edition stage II or IIIa according to anatomic staging table at diagnosis
* Patients without nodal involvement (cN0) are eligible if T size \> 2.0 cm (T2-3)
* Patients with nodal involvement (cN1-2) are eligible if T1-3
* Patients with clinical T4 or N3 disease are not eligible
* Patient must be willing and able (i.e., have no contraindication) to receive standard adjuvant therapy, consisting of HER2-directed therapy, radiation (if indicated) and endocrine therapy (if ER+) if achieving pCR at surgery
* Patient with bilateral invasive breast cancers are eligible if both cancers are HER2-positive (as defined in 3.1.3) at least one meets protocol eligibility and neither cancer renders the patient ineligible (i.e. per eligibility 3.1.5)
* Patients with multiple ipsilateral invasive tumors are eligible as long as all tumors are HER2-positive, and at least one tumor focus meets eligibility criteria (per eligibility 3.1.5). Multiple lesions that appear part of the same index tumor do not require additional biopsy/HER2 testing. Multiple lesions that appear part of the same index tumor do not require additional biopsy/HER2 testing. However, even if biopsy is not deemed necessary, consideration should be given to placing a clip in any lesion that is 1 cm or further from the primary tumor to ensure that all tumor is removed at surgery AND that the pathologist can locate all primary sites of tumor to assess pathologic response at surgery.
* Patients with a history of other non-breast malignancies are eligible if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
* Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, and localized papillary or follicular thyroid cancer who have completed recommended treatment including surgery. Patients with any other cancers within the last 5 years are ineligible.
* Patents must have a left ventricular ejection fraction (LVEF) within normal institutional parameters (or \> 50%)
* Patients must not have \> grade 1 peripheral neuropathy of any etiology.
* Patients must have a bilateral mammogram and a diagnostic breast ultrasound \[on the side of the cancer(s)\] (with or without breast MRI) performed at screening. An axillary ultrasound on the side of the cancer(s) is also required. However, if a patient has a negative axillary physical exam and a baseline MRI without suspicious lymph nodes performed before axillary ultrasound, axillary ultrasound may be omitted. Comprehensive breast and axillary imaging must be performed within 42 days of registration (i.e. the patient's mammogram/ breast ultrasound /axillary ultrasound OR their breast MRI).
* Baseline imaging of the ipsilateral axilla by ultrasound or breast MRI is mandatory. For subjects with axillary lymph node(s) suspicious on clinical exam or imaging, patient must be willing to have a needle aspiration or core biopsy to determine the presence of metastatic disease in the lymph nodes. A clip must be placed in the involved axillary lymph node. (If there are more than 1 suspicious axillary nodes, only one clipped node is required).
* Patient of childbearing potential and sexually active patients must use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for 7 months after the last dose of study treatment.
* Patient must be willing and able to sign informed consent
* Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to protocol registration)
* Absolute neutrophil count \>= 1,500/mcL (obtained =\< 28 days prior to protocol registration)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to protocol registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (obtained =\< 28 days prior to protocol registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 28 days prior to protocol registration)
* Creatinine =\< 1.5 x institutional ULN (obtained =\< 28 days prior to protocol registration)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Exclusion Criteria:
* Patients must not have impaired decision-making capacity
* Patient must not have a history of any prior (ipsilateral or contralateral) invasive breast cancer
* One exception: a patient with a history of T1N0 triple negative breast cancer diagnosed more than 10 years earlier, who remains disease free is eligible
* Patient must not have prior ipsilateral ductal breast carcinoma in situ (DCIS). Patients with prior lobular breast carcinoma in situ (LCIS), atypical hyperplasia, other high risk benign lesions or contralateral DCIS (without evidence of microinvasion) are eligible
* NOTE: Patients currently receiving endocrine therapy for prior contralateral DCIS are eligible
* Patient must not have stage IV (metastatic) breast cancer
* Staging studies (computed tomography \[CT\] chest/abdomen/pelvis and a bone scan or positron emission tomography \[PET\]-CT scan) are required for stage III disease or those with abnormal baseline liver function tests (LFTs), symptoms (e.g. new bone pain) or abnormal physical exam findings (National Comprehensive Cancer Network \[NCCN\] guidelines version \[V\]1.2019)
* Patient must not have T4 and/or N3 disease, including inflammatory breast cancer
* Patient must not have any prior treatment for the current breast cancer, including surgery, chemotherapy, hormonal therapy, radiation or experimental therapy
* Patients must not have \> grade 1 peripheral neuropathy of any etiology
* Patient must not have a concurrent serious medical condition that would preclude completion of study therapy. For example, uncontrolled hypertension (systolic \> 180 mm Hg and/or diastolic \> 100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to registration, unstable angina, congestive heart failure (CHF) or serious cardiac arrhythmia requiring medication and other concurrent serious diseases that may interfere with planned treatment
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. Patients must also not expect to conceive from the time of registration, while on study treatment, and until at least 7 months after the last dose of study treatment. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
* All patients of childbearing potential is anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Inclusion Criteria
Inclusion Criteria:
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Patient must have histologically confirmed HER2-positive primary invasive breast carcinoma, determined by local testing. The tumor must have either HER2 IHC result of 3+ or HER2/CEP17 ratio \> 2 with \> 4.0 HER2 signals per cell by ISH. Tumors with HER2/CEP17 ISH ratio \< 2 are ineligible, even if HER2 copy number is \> 6, unless HER2 IHC result is 3+.
* Patients hormone receptor (estrogen receptor \[ER\] and progesterone receptor \[PR\]) status must be known and will be determined by local testing. Patients with either hormone receptor -positive or hormone receptor- negative HER2-positive breast cancer are eligible
* Patients must have AJCC 8th Edition stage II or IIIa according to anatomic staging table at diagnosis
* Patients without nodal involvement (cN0) are eligible if T size \> 2.0 cm (T2-3)
* Patients with nodal involvement (cN1-2) are eligible if T1-3
* Patients with clinical T4 or N3 disease are not eligible
* Patient must be willing and able (i.e., have no contraindication) to receive standard adjuvant therapy, consisting of HER2-directed therapy, radiation (if indicated) and endocrine therapy (if ER+) if achieving pCR at surgery
* Patient with bilateral invasive breast cancers are eligible if both cancers are HER2-positive (as defined in 3.1.3) at least one meets protocol eligibility and neither cancer renders the patient ineligible (i.e. per eligibility 3.1.5)
* Patients with multiple ipsilateral invasive tumors are eligible as long as all tumors are HER2-positive, and at least one tumor focus meets eligibility criteria (per eligibility 3.1.5). Multiple lesions that appear part of the same index tumor do not require additional biopsy/HER2 testing. Multiple lesions that appear part of the same index tumor do not require additional biopsy/HER2 testing. However, even if biopsy is not deemed necessary, consideration should be given to placing a clip in any lesion that is 1 cm or further from the primary tumor to ensure that all tumor is removed at surgery AND that the pathologist can locate all primary sites of tumor to assess pathologic response at surgery.
* Patients with a history of other non-breast malignancies are eligible if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
* Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, and localized papillary or follicular thyroid cancer who have completed recommended treatment including surgery. Patients with any other cancers within the last 5 years are ineligible.
* Patents must have a left ventricular ejection fraction (LVEF) within normal institutional parameters (or \> 50%)
* Patients must not have \> grade 1 peripheral neuropathy of any etiology.
* Patients must have a bilateral mammogram and a diagnostic breast ultrasound \[on the side of the cancer(s)\] (with or without breast MRI) performed at screening. An axillary ultrasound on the side of the cancer(s) is also required. However, if a patient has a negative axillary physical exam and a baseline MRI without suspicious lymph nodes performed before axillary ultrasound, axillary ultrasound may be omitted. Comprehensive breast and axillary imaging must be performed within 42 days of registration (i.e. the patient's mammogram/ breast ultrasound /axillary ultrasound OR their breast MRI).
* Baseline imaging of the ipsilateral axilla by ultrasound or breast MRI is mandatory. For subjects with axillary lymph node(s) suspicious on clinical exam or imaging, patient must be willing to have a needle aspiration or core biopsy to determine the presence of metastatic disease in the lymph nodes. A clip must be placed in the involved axillary lymph node. (If there are more than 1 suspicious axillary nodes, only one clipped node is required).
* Patient of childbearing potential and sexually active patients must use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for 7 months after the last dose of study treatment.
* Patient must be willing and able to sign informed consent
* Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to protocol registration)
* Absolute neutrophil count \>= 1,500/mcL (obtained =\< 28 days prior to protocol registration)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to protocol registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (obtained =\< 28 days prior to protocol registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 28 days prior to protocol registration)
* Creatinine =\< 1.5 x institutional ULN (obtained =\< 28 days prior to protocol registration)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Patient must have histologically confirmed HER2-positive primary invasive breast carcinoma, determined by local testing. The tumor must have either HER2 IHC result of 3+ or HER2/CEP17 ratio \> 2 with \> 4.0 HER2 signals per cell by ISH. Tumors with HER2/CEP17 ISH ratio \< 2 are ineligible, even if HER2 copy number is \> 6, unless HER2 IHC result is 3+.
* Patients hormone receptor (estrogen receptor \[ER\] and progesterone receptor \[PR\]) status must be known and will be determined by local testing. Patients with either hormone receptor -positive or hormone receptor- negative HER2-positive breast cancer are eligible
* Patients must have AJCC 8th Edition stage II or IIIa according to anatomic staging table at diagnosis
* Patients without nodal involvement (cN0) are eligible if T size \> 2.0 cm (T2-3)
* Patients with nodal involvement (cN1-2) are eligible if T1-3
* Patients with clinical T4 or N3 disease are not eligible
* Patient must be willing and able (i.e., have no contraindication) to receive standard adjuvant therapy, consisting of HER2-directed therapy, radiation (if indicated) and endocrine therapy (if ER+) if achieving pCR at surgery
* Patient with bilateral invasive breast cancers are eligible if both cancers are HER2-positive (as defined in 3.1.3) at least one meets protocol eligibility and neither cancer renders the patient ineligible (i.e. per eligibility 3.1.5)
* Patients with multiple ipsilateral invasive tumors are eligible as long as all tumors are HER2-positive, and at least one tumor focus meets eligibility criteria (per eligibility 3.1.5). Multiple lesions that appear part of the same index tumor do not require additional biopsy/HER2 testing. Multiple lesions that appear part of the same index tumor do not require additional biopsy/HER2 testing. However, even if biopsy is not deemed necessary, consideration should be given to placing a clip in any lesion that is 1 cm or further from the primary tumor to ensure that all tumor is removed at surgery AND that the pathologist can locate all primary sites of tumor to assess pathologic response at surgery.
* Patients with a history of other non-breast malignancies are eligible if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
* Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, and localized papillary or follicular thyroid cancer who have completed recommended treatment including surgery. Patients with any other cancers within the last 5 years are ineligible.
* Patents must have a left ventricular ejection fraction (LVEF) within normal institutional parameters (or \> 50%)
* Patients must not have \> grade 1 peripheral neuropathy of any etiology.
* Patients must have a bilateral mammogram and a diagnostic breast ultrasound \[on the side of the cancer(s)\] (with or without breast MRI) performed at screening. An axillary ultrasound on the side of the cancer(s) is also required. However, if a patient has a negative axillary physical exam and a baseline MRI without suspicious lymph nodes performed before axillary ultrasound, axillary ultrasound may be omitted. Comprehensive breast and axillary imaging must be performed within 42 days of registration (i.e. the patient's mammogram/ breast ultrasound /axillary ultrasound OR their breast MRI).
* Baseline imaging of the ipsilateral axilla by ultrasound or breast MRI is mandatory. For subjects with axillary lymph node(s) suspicious on clinical exam or imaging, patient must be willing to have a needle aspiration or core biopsy to determine the presence of metastatic disease in the lymph nodes. A clip must be placed in the involved axillary lymph node. (If there are more than 1 suspicious axillary nodes, only one clipped node is required).
* Patient of childbearing potential and sexually active patients must use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for 7 months after the last dose of study treatment.
* Patient must be willing and able to sign informed consent
* Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to protocol registration)
* Absolute neutrophil count \>= 1,500/mcL (obtained =\< 28 days prior to protocol registration)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to protocol registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (obtained =\< 28 days prior to protocol registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 28 days prior to protocol registration)
* Creatinine =\< 1.5 x institutional ULN (obtained =\< 28 days prior to protocol registration)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04266249
Org Class
Network
Org Full Name
Eastern Cooperative Oncology Group
Org Study Id
EA1181
Overall Status
Active, not recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
(CompassHER2-pCR): Preoperative THP and Postoperative HP in Patients Who Achieve a Pathologic Complete Response
Primary Outcomes
Outcome Description
Events include recurrence of ipsilateral invasive breast tumor, recurrence of locoregional invasive breast tumor, and distant recurrence. Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and estrogen receptor (ER) status. Greenwood method will be used to estimate the 95% confidence interval for 3-year rate.
Outcome Measure
Recurrence-free survival (RFS)
Outcome Time Frame
Up to 3 years after end of treatment
Secondary Ids
Secondary Id
NCI-2019-07439
Secondary Id
EA1181
Secondary Id
EA1181
Secondary Id
U10CA180820
Secondary Outcomes
Outcome Description
Events include recurrence of ipsilateral invasive breast tumor, recurrence of locoregional invasive breast tumor, distant recurrence, contralateral invasive breast cancer, and second primary non-breast invasive cancer (other than squamous or basal cell skin cancer). Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.
Outcome Time Frame
Up to 3 years after the end of treatment
Outcome Measure
Invasive disease-free survival (IDFS)
Outcome Description
Events include distant recurrence and second primary non-breast invasive cancer (other than squamous or basal cell skin cancer). Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.
Outcome Time Frame
Up to 3 years after the end of treatment
Outcome Measure
Distant disease-free survival (DDFS)
Outcome Description
Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.
Outcome Time Frame
U to 3 years after the end of treatment
Outcome Measure
Distant relapse-free survival (DRFS)
Outcome Description
Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.
Outcome Time Frame
Up to 3 years after the end of treatment
Outcome Measure
Recurrence-free interval (RFI)
Outcome Description
Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.
Outcome Time Frame
From date of surgery until the date of death from any cause, assessed up to 3 years after the end of treatment
Outcome Measure
Overall survival (OS)
Outcome Description
Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.
Outcome Time Frame
Up to 3 years after the end of treatment
Outcome Measure
Event-free survival (EFS)
Outcome Description
Will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. All treatment-emergent and baseline adverse events and hematological/biochemical toxicities based on laboratory measurements, as well as drug related AEs, will be summarized by NCI CTCAE v5.0 worst grade. The incidence of deaths and treatment-emergent serious adverse events (defined as number of patients experiencing the AE divided by all treated patients) will be summarized using binominal proportions and binomial exact 95% confidence intervals. The incidence of adverse events leading to discontinuation of protocol therapy will be summarized and listed as well.
Outcome Time Frame
Up to 1 week after cycle 4 (all patients) and/or up to cycle 13 post-surgery (Arm A only) (each cycle is 21 days)
Outcome Measure
Incidence of adverse events (AEs)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Della Makower
Investigator Email
DMAKOWER@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
MeSH Terms
DOCETAXEL
MASTECTOMY, SEGMENTAL
MASTECTOMY
130-NM ALBUMIN-BOUND PACLITAXEL
ALBUMIN-BOUND PACLITAXEL
PACLITAXEL
PERTUZUMAB
2C4 ANTIBODY
RADIOTHERAPY
ELECTROMAGNETIC RADIATION
RADIATION
TRASTUZUMAB
PF-05280014
OGIVRI
ONTRUZANT
TRASTUZUMAB BIOSIMILAR HLX02
ADO-TRASTUZUMAB EMTANSINE
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ORGANIC CHEMICALS
DITERPENES
TERPENES
SURGICAL PROCEDURES, OPERATIVE
ALBUMINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
THERAPEUTICS
ELECTROMAGNETIC PHENOMENA
MAGNETIC PHENOMENA
PHYSICAL PHENOMENA
ANTIBODIES, MONOCLONAL, HUMANIZED
ANTIBODIES, MONOCLONAL
ANTIBODIES
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
SERUM GLOBULINS
GLOBULINS
MAYTANSINE
MACROLIDES
LACTONES
LACTAMS, MACROCYCLIC
MACROCYCLIC COMPOUNDS
POLYCYCLIC COMPOUNDS