Brief Summary
This randomized phase III trial studies how well giving cisplatin and radiation therapy together with or without carboplatin and paclitaxel works in treating patients with cervical cancer has spread from where it started to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as cisplatin, carboplatin, and paclitaxel, work in different ways to stop the growth of \[cancer/tumor\] cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. External radiation therapy uses high-energy x rays to kill tumor cells. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. It is not yet known whether giving cisplatin and external and internal radiation therapy together with carboplatin and paclitaxel kills more tumor cells.
Brief Title
Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer
Detailed Description
PRIMARY OBJECTIVES:
I. To determine if the addition of adjuvant chemotherapy to standard cisplatin-based chemoradiation improves overall survival.
SECONDARY OBJECTIVES:
I. To determine the progression-free survival rates. II. To determine acute and long-term toxicities. III. To determine patterns of disease recurrence. IV. To determine the association between radiation protocol compliance and outcomes.
V. To determine patient quality of life, including psycho-sexual health.
TERTIARY OBJECTIVES:
I. To determine the association between the results of a follow-up positron emission tomography (PET) scan performed 4-6 months post completion of chemoradiation and outcomes for all patients in the trial.
II. To determine the biological predictors of patients' outcomes based on translational laboratory studies of blood and tissue specimens.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive cisplatin intravenously (IV) over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate, pulsed-dose rate, or low-dose rate intracavitary brachytherapy.
ARM II: Patients receive cisplatin and undergo external-beam radiation and brachytherapy as in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients may undergo baseline tumor biopsy and blood collection for future correlative studies.
Patients complete the European Organization for Research and Treatment of Cancer (EORTC) Core questionnaire (QLQ-C30), the EORTC cervix cancer module (CX24), the ovarian cancer module (OV28), and the Sexual function-Vaginal Changes Questionnaire (SVQ) questionnaires at baseline, during, and after completion of study treatment.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
I. To determine if the addition of adjuvant chemotherapy to standard cisplatin-based chemoradiation improves overall survival.
SECONDARY OBJECTIVES:
I. To determine the progression-free survival rates. II. To determine acute and long-term toxicities. III. To determine patterns of disease recurrence. IV. To determine the association between radiation protocol compliance and outcomes.
V. To determine patient quality of life, including psycho-sexual health.
TERTIARY OBJECTIVES:
I. To determine the association between the results of a follow-up positron emission tomography (PET) scan performed 4-6 months post completion of chemoradiation and outcomes for all patients in the trial.
II. To determine the biological predictors of patients' outcomes based on translational laboratory studies of blood and tissue specimens.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive cisplatin intravenously (IV) over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate, pulsed-dose rate, or low-dose rate intracavitary brachytherapy.
ARM II: Patients receive cisplatin and undergo external-beam radiation and brachytherapy as in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients may undergo baseline tumor biopsy and blood collection for future correlative studies.
Patients complete the European Organization for Research and Treatment of Cancer (EORTC) Core questionnaire (QLQ-C30), the EORTC cervix cancer module (CX24), the ovarian cancer module (OV28), and the Sexual function-Vaginal Changes Questionnaire (SVQ) questionnaires at baseline, during, and after completion of study treatment.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Cervical Adenocarcinoma
Cervical Adenosquamous Carcinoma
Cervical Squamous Cell Carcinoma, Not Otherwise Specified
Stage IB Cervical Cancer AJCC v6 and v7
Stage IIA Cervical Cancer AJCC v7
Stage IIB Cervical Cancer AJCC v6 and v7
Stage IIIB Cervical Cancer AJCC v6 and v7
Stage IVA Cervical Cancer AJCC v6 and v7
Eligibility Criteria
Inclusion Criteria:
* Eligible patients will have locally advanced cervical cancer suitable for primary treatment with chemoradiation with curative intent, in addition to:
* Federation of Gynecology and Obstetrics (FIGO) 2008 stage IB1 \& node positive, IB2, IIA, IIB, IIIB, or IVA disease
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix
* White blood cells (WBC) \>= 3.0 x 10\^9/L
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
* Platelet count \>= 100 x 10\^9/L
* Bilirubin =\< 1.5 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 2.5 x ULN (if both tests are done, both results need to be =\< 2.5 x ULN)
* Creatinine =\< ULN (Common Toxicity Criteria \[CTC\] grade 0) OR calculated creatinine clearance (Cockcroft-Gault formula) \>= 60 mL/min OR \>= 50 mL/min by ethylenediaminetetraacetic acid (EDTA) creatinine clearance
* Written informed consent
Exclusion Criteria:
* Any previous pelvic radiotherapy
* Para-aortic nodal involvement above the level of the common iliac nodes or L3/L4 (if biopsy proven, PET positive, or \>= 15 mm short-axis diameter on computed tomography \[CT\])
* FIGO 2008 stage IIIA disease
* Patients assessed at presentation as requiring interstitial brachytherapy treatment
* Patients with bilateral hydronephrosis unless at least one side has been stented and renal function fulfills the required inclusion criteria
* Previous chemotherapy for this tumor
* Evidence of distant metastases
* Prior diagnosis of Crohn's disease or ulcerative colitis
* Peripheral neuropathy \>= grade 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]4)
* Patients who have undergone a previous hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy; this includes patients with a prior history of supracervical hysterectomy
* Patients with other invasive malignancies, with the exception of non-melanoma skin cancer and in situ melanoma, who had (or have) any evidence of the other cancer present within the last 5 years
* Patients who are pregnant or lactating
* Any contraindication to the use of cisplatin, carboplatin, or paclitaxel chemotherapy
* Serious illness or medical condition that precludes the safe administration of the trial treatment including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Patients who are known to be human immunodeficiency virus (HIV) positive
* Eligible patients will have locally advanced cervical cancer suitable for primary treatment with chemoradiation with curative intent, in addition to:
* Federation of Gynecology and Obstetrics (FIGO) 2008 stage IB1 \& node positive, IB2, IIA, IIB, IIIB, or IVA disease
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix
* White blood cells (WBC) \>= 3.0 x 10\^9/L
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
* Platelet count \>= 100 x 10\^9/L
* Bilirubin =\< 1.5 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 2.5 x ULN (if both tests are done, both results need to be =\< 2.5 x ULN)
* Creatinine =\< ULN (Common Toxicity Criteria \[CTC\] grade 0) OR calculated creatinine clearance (Cockcroft-Gault formula) \>= 60 mL/min OR \>= 50 mL/min by ethylenediaminetetraacetic acid (EDTA) creatinine clearance
* Written informed consent
Exclusion Criteria:
* Any previous pelvic radiotherapy
* Para-aortic nodal involvement above the level of the common iliac nodes or L3/L4 (if biopsy proven, PET positive, or \>= 15 mm short-axis diameter on computed tomography \[CT\])
* FIGO 2008 stage IIIA disease
* Patients assessed at presentation as requiring interstitial brachytherapy treatment
* Patients with bilateral hydronephrosis unless at least one side has been stented and renal function fulfills the required inclusion criteria
* Previous chemotherapy for this tumor
* Evidence of distant metastases
* Prior diagnosis of Crohn's disease or ulcerative colitis
* Peripheral neuropathy \>= grade 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]4)
* Patients who have undergone a previous hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy; this includes patients with a prior history of supracervical hysterectomy
* Patients with other invasive malignancies, with the exception of non-melanoma skin cancer and in situ melanoma, who had (or have) any evidence of the other cancer present within the last 5 years
* Patients who are pregnant or lactating
* Any contraindication to the use of cisplatin, carboplatin, or paclitaxel chemotherapy
* Serious illness or medical condition that precludes the safe administration of the trial treatment including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Patients who are known to be human immunodeficiency virus (HIV) positive
Inclusion Criteria
Inclusion Criteria:
* Eligible patients will have locally advanced cervical cancer suitable for primary treatment with chemoradiation with curative intent, in addition to:
* Federation of Gynecology and Obstetrics (FIGO) 2008 stage IB1 \& node positive, IB2, IIA, IIB, IIIB, or IVA disease
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix
* White blood cells (WBC) \>= 3.0 x 10\^9/L
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
* Platelet count \>= 100 x 10\^9/L
* Bilirubin =\< 1.5 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 2.5 x ULN (if both tests are done, both results need to be =\< 2.5 x ULN)
* Creatinine =\< ULN (Common Toxicity Criteria \[CTC\] grade 0) OR calculated creatinine clearance (Cockcroft-Gault formula) \>= 60 mL/min OR \>= 50 mL/min by ethylenediaminetetraacetic acid (EDTA) creatinine clearance
* Written informed consent
* Eligible patients will have locally advanced cervical cancer suitable for primary treatment with chemoradiation with curative intent, in addition to:
* Federation of Gynecology and Obstetrics (FIGO) 2008 stage IB1 \& node positive, IB2, IIA, IIB, IIIB, or IVA disease
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix
* White blood cells (WBC) \>= 3.0 x 10\^9/L
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
* Platelet count \>= 100 x 10\^9/L
* Bilirubin =\< 1.5 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 2.5 x ULN (if both tests are done, both results need to be =\< 2.5 x ULN)
* Creatinine =\< ULN (Common Toxicity Criteria \[CTC\] grade 0) OR calculated creatinine clearance (Cockcroft-Gault formula) \>= 60 mL/min OR \>= 50 mL/min by ethylenediaminetetraacetic acid (EDTA) creatinine clearance
* Written informed consent
Gender
Female
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
NCT01414608
Org Class
Network
Org Full Name
GOG Foundation
Org Study Id
ANZGOG-0902-GOG-0274
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase III Trial of Adjuvant Chemotherapy Following Chemoradiation as Primary Treatment for Locally Advanced Cervical Cancer Compared to Chemoradiation Alone: The OUTBACK Trial
Primary Outcomes
Outcome Description
Estimate for probability of overall survival at 5 years by Kaplan-Meier method, where overall survival is defined as the time from randomization to time of death due to any cause or the date of last contact, whichever occurs first.
Outcome Measure
Overall Survival Rate at 5 Years
Outcome Time Frame
5 years from study randomization
Secondary Ids
Secondary Id
NCI-2011-02978
Secondary Id
ANZGOG-0902/GOG-0274/RTOG-1174
Secondary Id
CDR0000706698
Secondary Id
GOG-0274
Secondary Id
RTOG-1174
Secondary Id
ANZGOG-0902
Secondary Id
S12-01864
Secondary Id
ANZGOG-0902-GOG-0274
Secondary Id
ANZGOG-0902-GOG-0274
Secondary Id
U10CA180868
Secondary Id
U10CA027469
Secondary Outcomes
Outcome Description
Estimate for probability of progression free at 5 years by Kaplan-Meier method, where progression-free survival is defined as the time from randomization to the time of disease progression, death from any cause or date of last contact, whichever occurs first. Disease progression is defined by increasing clinical, radiological or pathological evidence of disease from participant entry to when investigator deems a progression. RECIST V1.0 was not used to determine response on this study.
Outcome Time Frame
5 years from study randomization
Outcome Measure
Progression-free Survival Rate at 5 Years
Outcome Description
Number of participants with a maximum grade of 3 or higher for pre-specified adverse events that occurred during the first year after randomization. Adverse events are graded and categorized using CTCAE v4.0.
Outcome Time Frame
1 year after randomization
Outcome Measure
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year
Outcome Description
Number of patients for the site of disease recurrence. Disease was considered as persistent if participant had evidence of disease at study entry and disease did not progress during study. Disease status was considered locoregional alone if a participant had disease progression in the pelvis region including vagina after study entry. Disease status was considered distant if a participant had disease progression outside the pelvis (for example the abdomen and lung) after study entry. Criteria used to determine the no progression group includes participants that expired without documentation of progression.
Outcome Time Frame
through study completion an average of 60 months
Outcome Measure
Patterns of Disease Recurrence
Outcome Description
Radiation protocol compliance measured by external beam dose delivered
Outcome Time Frame
Average duration of 7 weeks
Outcome Measure
Radiation Protocol Compliance
Outcome Description
Quality of Life measured by change of global health status score from baseline to 12 months follow-up. A cancer-specific questionnaire with 30 items which summarize as five functioning scales, a global health status/quality of life scale, three symptom scales and six single items assessing additional symptoms and perceived financial impact. The minimum global health status score was 0 and the maximum global health status score was 100. A higher global health status score means better outcome.
Outcome Time Frame
Baseline and 12 months
Outcome Measure
Quality of Life for Global Health Status
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
Gary Goldberg
Investigator Email
ggoldber@montefiore.org
Investigator Phone
718-904-2893
Categories Mesh Debug
Prostate Cancer --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Gynecologic Cancers --- UTERINE CERVICAL DISEASES
Gynecologic Cancers --- UTERINE DISEASES
MeSH Terms
UTERINE CERVICAL NEOPLASMS
UTERINE NEOPLASMS
GENITAL NEOPLASMS, FEMALE
UROGENITAL NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
UTERINE CERVICAL DISEASES
UTERINE DISEASES
GENITAL DISEASES, FEMALE
FEMALE UROGENITAL DISEASES
FEMALE UROGENITAL DISEASES AND PREGNANCY COMPLICATIONS
UROGENITAL DISEASES
GENITAL DISEASES
BRACHYTHERAPY
CARBOPLATIN
CISPLATIN
1,2-DIAMINOCYCLOHEXANEPLATINUM II CITRATE
PLATINUM
RADIATION
PACLITAXEL
ALBUMIN-BOUND PACLITAXEL
RADIOTHERAPY
THERAPEUTICS
COORDINATION COMPLEXES
ORGANIC CHEMICALS
CHLORINE COMPOUNDS
INORGANIC CHEMICALS
NITROGEN COMPOUNDS
PLATINUM COMPOUNDS
METALS, HEAVY
ELEMENTS
TRANSITION ELEMENTS
METALS
PHYSICAL PHENOMENA
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
DITERPENES
TERPENES
ALBUMINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS