Brief Summary
This randomized phase II trial studies how well fludeoxyglucose F-18 (FDG)/positron emission tomography (PET) directed treatment improves response in patients with stomach or gastroesophageal junction cancer that has not spread past the stomach and is not responding to the usual treatment. PET scans are a different way to take pictures of cancer and can be used to look at how much energy (such as glucose) is being used by the cancer. Using PET scans early to monitor the success of treatment may allow doctors to measure response and change treatment accordingly.
Brief Title
FDG-PET Directed Treatment in Improving Response in Patients With Locally Advanced Stomach or Gastroesophageal Junction Cancer
Detailed Description
Pre-registered patients receive standard pre-operative chemotherapy comprising epirubicin intravenously 50mg/m\^2 (IV) on day 1; oxaliplatin 130 mg/m\^2 IV or cisplatin 60 mg/m\^2 IV on day 1; and capecitabine 625 mg/m\^2 orally (PO) twice daily (BID) or fluorouracil 200 mg/m\^2/day IV continuously on days 1-21; and undergo FDG-PET following course 1 (days 15-19). Patients defined as FDG-PET non-responders are registered and randomized to 1 of 2 treatment arms.
Primary objective
To assess and compare the overall survival (OS) of patients with locally advanced gastric cancer classified as FDG-PET non-responders after one cycle of pre-operative chemotherapy randomly assigned to receive either salvage chemotherapy before and after surgery or immediate surgery followed by fluorouracil sensitized radiotherapy.
Secondary objectives
1. To assess and compare progression-free survival (PFS) between the treatment arms (Arms A and B).
2. To assess and compare R0 resection rate between the treatment arms (Arms A and B).
3. To assess and compare pathologic complete response (pCR) rate between the treatment arms (Arms A and B).
4. To assess the adverse events (AE) profile and safety of each treatment arm (Arms A and B), including post-operative mortality rate, 30-day post-operative targeted adverse events (i.e., dehiscence, significant infection, and re-operation rate).
5. To examine the changes of FDG-PET SUV induced by pre-operative chemotherapy at different time points (from baseline to completion of one cycle of treatment before randomization, and 2 cycles of salvage treatment) in patients randomized to salvage treatment arm (Arm B).
6. To collect measurement of fatigue and overall perception of QOL at registration of the study (Alliance registration QOL assessment study).
Primary objective
To assess and compare the overall survival (OS) of patients with locally advanced gastric cancer classified as FDG-PET non-responders after one cycle of pre-operative chemotherapy randomly assigned to receive either salvage chemotherapy before and after surgery or immediate surgery followed by fluorouracil sensitized radiotherapy.
Secondary objectives
1. To assess and compare progression-free survival (PFS) between the treatment arms (Arms A and B).
2. To assess and compare R0 resection rate between the treatment arms (Arms A and B).
3. To assess and compare pathologic complete response (pCR) rate between the treatment arms (Arms A and B).
4. To assess the adverse events (AE) profile and safety of each treatment arm (Arms A and B), including post-operative mortality rate, 30-day post-operative targeted adverse events (i.e., dehiscence, significant infection, and re-operation rate).
5. To examine the changes of FDG-PET SUV induced by pre-operative chemotherapy at different time points (from baseline to completion of one cycle of treatment before randomization, and 2 cycles of salvage treatment) in patients randomized to salvage treatment arm (Arm B).
6. To collect measurement of fatigue and overall perception of QOL at registration of the study (Alliance registration QOL assessment study).
Categories
Completion Date
Completion Date Type
Actual
Conditions
Adenocarcinoma of the Gastroesophageal Junction
Gastric Adenocarcinoma
Gastric Cancer
Eligibility Criteria
Pre-Registration Eligibility Criteria
1. Documentation of Disease
1.1 Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II, III)
1.2 Pre-treatment clinical stage of T3-4N any M0 or T any N positive M0 as determined by laparoscopy, CT scan (or PET/CT), or endoscopic ultrasound (histologic confirmation of lymph involvement is not required). Therefore, patients can have measurable or non-measurable disease.
1.3 Patients with T1-2N0M0 tumors or patients with metastatic disease are NOT eligible.
2. Patients must be eligible for curative intent surgical resection.
3. FDG Avid malignancy - Patients must have an FDG avid tumor(s). FDG avid tumors are defined as a primary tumor with an increased uptake in the region of the tumor that has an SUV of \> 5.0 or a tumor:liver SUV ratio of \> 1.5.
4. No prior history of congestive heart failure - NYHA class I to IV or known DPD deficiency
5. No current grade 2, 3, or 4 of neuropathy.
6. No known hypersensitivity to epirubicin, oxaliplatin and cisplatin, capecitabine and 5-flurouracil, docetaxel or irinotecan.
7. Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects.
7.1 Therefore, for women of childbearing potential only, a negative serum pregnancy test pregnancy test done ≤ 7 days prior to pre-registration is required.
7.2 A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
8. Age ≥ 18 years
9. ECOG Performance Status 0 or 1
10. Required Initial Laboratory Values:
* Absolute Neutrophil Count (ANC) ≥ 1,500/mm\^3
* Platelet Count ≥ 100,000/mm\^3
* Creatinine ≤ 1.5 x upper limit of normal (ULN)
* Total Bilirubin ≤ 1.5 x ULN, except in patients with Gilbert's disease
* AST and ALT ≤ 2.5 x ULN
* Alkaline Phosphatase ≤ 2.5 x ULN
Registration Eligibility Criteria to Treatment Arms A or B
1. Patient must continue to be eligible for curative intent surgical resection.
2. Disease Progression: FDG avid malignancy that is classified as an FDG PET non- responder. PET non-responders are defined as having \< 35% reduction in the FDG uptake of the primary tumor when compared to baseline.
3. Concomitant Medications -
3.1 Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this trial. Patients on strong CYP3A4 inhibitors must discontinue the drug 14 days prior to the start of study treatment.
3.2 Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.
4. Patient must have received only one cycle of the following regimens during the pre-registration time period and no other therapy for gastric or gastroesophageal junction cancer:
* Epirubicin, Oxaliplatin, and Capecitabine
* Epirubicin, Oxaliplatin, and Fluorouracil
* Epirubicin, Cisplatin, and Capecitabine
* Epirubicin, Cisplatin, and Fluorouracil
5. Toxicity recovery should include the following:
* Grade ≤ 2 neuropathy
* Grade ≤ 2 diarrhea
* Grade ≤ 2 mucositis
6. Pre-registration chemotherapy given within 42 days of treatment (treatment meaning surgery if Arm A, chemotherapy if Arm B)
1. Documentation of Disease
1.1 Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II, III)
1.2 Pre-treatment clinical stage of T3-4N any M0 or T any N positive M0 as determined by laparoscopy, CT scan (or PET/CT), or endoscopic ultrasound (histologic confirmation of lymph involvement is not required). Therefore, patients can have measurable or non-measurable disease.
1.3 Patients with T1-2N0M0 tumors or patients with metastatic disease are NOT eligible.
2. Patients must be eligible for curative intent surgical resection.
3. FDG Avid malignancy - Patients must have an FDG avid tumor(s). FDG avid tumors are defined as a primary tumor with an increased uptake in the region of the tumor that has an SUV of \> 5.0 or a tumor:liver SUV ratio of \> 1.5.
4. No prior history of congestive heart failure - NYHA class I to IV or known DPD deficiency
5. No current grade 2, 3, or 4 of neuropathy.
6. No known hypersensitivity to epirubicin, oxaliplatin and cisplatin, capecitabine and 5-flurouracil, docetaxel or irinotecan.
7. Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects.
7.1 Therefore, for women of childbearing potential only, a negative serum pregnancy test pregnancy test done ≤ 7 days prior to pre-registration is required.
7.2 A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
8. Age ≥ 18 years
9. ECOG Performance Status 0 or 1
10. Required Initial Laboratory Values:
* Absolute Neutrophil Count (ANC) ≥ 1,500/mm\^3
* Platelet Count ≥ 100,000/mm\^3
* Creatinine ≤ 1.5 x upper limit of normal (ULN)
* Total Bilirubin ≤ 1.5 x ULN, except in patients with Gilbert's disease
* AST and ALT ≤ 2.5 x ULN
* Alkaline Phosphatase ≤ 2.5 x ULN
Registration Eligibility Criteria to Treatment Arms A or B
1. Patient must continue to be eligible for curative intent surgical resection.
2. Disease Progression: FDG avid malignancy that is classified as an FDG PET non- responder. PET non-responders are defined as having \< 35% reduction in the FDG uptake of the primary tumor when compared to baseline.
3. Concomitant Medications -
3.1 Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this trial. Patients on strong CYP3A4 inhibitors must discontinue the drug 14 days prior to the start of study treatment.
3.2 Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.
4. Patient must have received only one cycle of the following regimens during the pre-registration time period and no other therapy for gastric or gastroesophageal junction cancer:
* Epirubicin, Oxaliplatin, and Capecitabine
* Epirubicin, Oxaliplatin, and Fluorouracil
* Epirubicin, Cisplatin, and Capecitabine
* Epirubicin, Cisplatin, and Fluorouracil
5. Toxicity recovery should include the following:
* Grade ≤ 2 neuropathy
* Grade ≤ 2 diarrhea
* Grade ≤ 2 mucositis
6. Pre-registration chemotherapy given within 42 days of treatment (treatment meaning surgery if Arm A, chemotherapy if Arm B)
Inclusion Criteria
Pre-Registration Eligibility Criteria
1. Documentation of Disease
1.1 Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II, III)
1.2 Pre-treatment clinical stage of T3-4N any M0 or T any N positive M0 as determined by laparoscopy, CT scan (or PET/CT), or endoscopic ultrasound (histologic confirmation of lymph involvement is not required). Therefore, patients can have measurable or non-measurable disease.
1.3 Patients with T1-2N0M0 tumors or patients with metastatic disease are NOT eligible.
2. Patients must be eligible for curative intent surgical resection.
3. FDG Avid malignancy - Patients must have an FDG avid tumor(s). FDG avid tumors are defined as a primary tumor with an increased uptake in the region of the tumor that has an SUV of \> 5.0 or a tumor:liver SUV ratio of \> 1.5.
4. No prior history of congestive heart failure - NYHA class I to IV or known DPD deficiency
5. No current grade 2, 3, or 4 of neuropathy.
6. No known hypersensitivity to epirubicin, oxaliplatin and cisplatin, capecitabine and 5-flurouracil, docetaxel or irinotecan.
7. Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects.
7.1 Therefore, for women of childbearing potential only, a negative serum pregnancy test pregnancy test done ≤ 7 days prior to pre-registration is required.
7.2 A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
8. Age ≥ 18 years
9. ECOG Performance Status 0 or 1
10. Required Initial Laboratory Values:
* Absolute Neutrophil Count (ANC) ≥ 1,500/mm\^3
* Platelet Count ≥ 100,000/mm\^3
* Creatinine ≤ 1.5 x upper limit of normal (ULN)
* Total Bilirubin ≤ 1.5 x ULN, except in patients with Gilbert's disease
* AST and ALT ≤ 2.5 x ULN
* Alkaline Phosphatase ≤ 2.5 x ULN
Registration Eligibility Criteria to Treatment Arms A or B
1. Patient must continue to be eligible for curative intent surgical resection.
2. Disease Progression: FDG avid malignancy that is classified as an FDG PET non- responder. PET non-responders are defined as having \< 35% reduction in the FDG uptake of the primary tumor when compared to baseline.
3. Concomitant Medications -
3.1 Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this trial. Patients on strong CYP3A4 inhibitors must discontinue the drug 14 days prior to the start of study treatment.
3.2 Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.
4. Patient must have received only one cycle of the following regimens during the pre-registration time period and no other therapy for gastric or gastroesophageal junction cancer:
* Epirubicin, Oxaliplatin, and Capecitabine
* Epirubicin, Oxaliplatin, and Fluorouracil
* Epirubicin, Cisplatin, and Capecitabine
* Epirubicin, Cisplatin, and Fluorouracil
5. Toxicity recovery should include the following:
* Grade ≤ 2 neuropathy
* Grade ≤ 2 diarrhea
* Grade ≤ 2 mucositis
6. Pre-registration chemotherapy given within 42 days of treatment (treatment meaning surgery if Arm A, chemotherapy if Arm B)
1. Documentation of Disease
1.1 Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II, III)
1.2 Pre-treatment clinical stage of T3-4N any M0 or T any N positive M0 as determined by laparoscopy, CT scan (or PET/CT), or endoscopic ultrasound (histologic confirmation of lymph involvement is not required). Therefore, patients can have measurable or non-measurable disease.
1.3 Patients with T1-2N0M0 tumors or patients with metastatic disease are NOT eligible.
2. Patients must be eligible for curative intent surgical resection.
3. FDG Avid malignancy - Patients must have an FDG avid tumor(s). FDG avid tumors are defined as a primary tumor with an increased uptake in the region of the tumor that has an SUV of \> 5.0 or a tumor:liver SUV ratio of \> 1.5.
4. No prior history of congestive heart failure - NYHA class I to IV or known DPD deficiency
5. No current grade 2, 3, or 4 of neuropathy.
6. No known hypersensitivity to epirubicin, oxaliplatin and cisplatin, capecitabine and 5-flurouracil, docetaxel or irinotecan.
7. Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects.
7.1 Therefore, for women of childbearing potential only, a negative serum pregnancy test pregnancy test done ≤ 7 days prior to pre-registration is required.
7.2 A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
8. Age ≥ 18 years
9. ECOG Performance Status 0 or 1
10. Required Initial Laboratory Values:
* Absolute Neutrophil Count (ANC) ≥ 1,500/mm\^3
* Platelet Count ≥ 100,000/mm\^3
* Creatinine ≤ 1.5 x upper limit of normal (ULN)
* Total Bilirubin ≤ 1.5 x ULN, except in patients with Gilbert's disease
* AST and ALT ≤ 2.5 x ULN
* Alkaline Phosphatase ≤ 2.5 x ULN
Registration Eligibility Criteria to Treatment Arms A or B
1. Patient must continue to be eligible for curative intent surgical resection.
2. Disease Progression: FDG avid malignancy that is classified as an FDG PET non- responder. PET non-responders are defined as having \< 35% reduction in the FDG uptake of the primary tumor when compared to baseline.
3. Concomitant Medications -
3.1 Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this trial. Patients on strong CYP3A4 inhibitors must discontinue the drug 14 days prior to the start of study treatment.
3.2 Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.
4. Patient must have received only one cycle of the following regimens during the pre-registration time period and no other therapy for gastric or gastroesophageal junction cancer:
* Epirubicin, Oxaliplatin, and Capecitabine
* Epirubicin, Oxaliplatin, and Fluorouracil
* Epirubicin, Cisplatin, and Capecitabine
* Epirubicin, Cisplatin, and Fluorouracil
5. Toxicity recovery should include the following:
* Grade ≤ 2 neuropathy
* Grade ≤ 2 diarrhea
* Grade ≤ 2 mucositis
6. Pre-registration chemotherapy given within 42 days of treatment (treatment meaning surgery if Arm A, chemotherapy if Arm B)
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
NCT02485834
Org Class
Other
Org Full Name
Alliance for Clinical Trials in Oncology
Org Study Id
A021302
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Impact of Early FDG-PET Directed Intervention on Preoperative Therapy for Locally Advanced Gastric Cancer: A Random Assignment Phase II Study
Primary Outcomes
Outcome Description
Overall survival is defined as the time from date of randomization to death due to any cause.
Outcome Measure
Overall Survival
Outcome Time Frame
Up to 3 years
Secondary Ids
Secondary Id
U10CA180821
Secondary Id
NCI-2014-02566
Secondary Outcomes
Outcome Description
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Outcome Time Frame
Up to 3 years
Outcome Measure
Progression-free Survival
Outcome Description
The number of patients achieved R0 resection during surgery
Outcome Time Frame
At time of surgery
Outcome Measure
Number of Patients Achieved R0 Resection During Surgery
Outcome Description
The number of patients had pathologic complete response (pCR). (pCR is defined as no gross or microscopic tumor identified with the surgical specimen. All lymph nodes should be free of tumor to document a PCR. If no gross tumor is visible, section around the area of inflammation (nodularity) should be made every 2-3 cm and specimens examined.)
Outcome Time Frame
Up to 3 years
Outcome Measure
Number of Patients Had Pathologic Complete Response
Outcome Description
The number of patients who reported grade 3 or higher Adverse Events according to Common Terminology Criteria for Adverse Events version 4.0.
Outcome Time Frame
Up to 30 days after completion of protocol treatment
Outcome Measure
Number of Participants Who Reported Grade 3 or Higher Adverse Events
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
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
Haejin In
Investigator Email
hin@montefiore.org
Investigator Phone
929-246-6726
Categories Mesh Debug
Gastrointestinal (GI) Cancers --- GASTROINTESTINAL NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Gastrointestinal (GI) Cancers --- GASTROINTESTINAL DISEASES
Digestive System --- GASTROINTESTINAL DISEASES
Gastrointestinal (GI) Cancers --- STOMACH DISEASES
Gastrointestinal (GI) Cancers --- CAPECITABINE
MeSH Terms
STOMACH NEOPLASMS
GASTROINTESTINAL NEOPLASMS
DIGESTIVE SYSTEM NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
DIGESTIVE SYSTEM DISEASES
GASTROINTESTINAL DISEASES
STOMACH DISEASES
SURGICAL PROCEDURES, OPERATIVE
FLUOROURACIL
CAPECITABINE
DOCETAXEL
IRINOTECAN
RADIOTHERAPY, CONFORMAL
URACIL
PYRIMIDINONES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
DEOXYRIBONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ORGANIC CHEMICALS
DITERPENES
TERPENES
CAMPTOTHECIN
ALKALOIDS
RADIOTHERAPY, COMPUTER-ASSISTED
RADIOTHERAPY
THERAPEUTICS