This randomized phase III trial studies the side effects of paclitaxel when given together with cisplatin or topotecan with or without bevacizumab and to compare how well they work in treating patients with stage IVB, cervical cancer that has come back or is persistent. Drugs used in chemotherapy, such as paclitaxel, cisplatin, and topotecan, 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. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether paclitaxel is more effective when given together with cisplatin or topotecan with or without bevacizumab in treating patients with cervical cancer.
PRIMARY OBJECTIVES: I. To determine whether the addition of bevacizumab to chemotherapy improves overall survival. Also to determine if a regimen involving paclitaxel and topotecan improves overall survival in comparison to a regimen involving cisplatin and paclitaxel. These regimens are to be evaluated in patients with stage IVB, recurrent, or persistent carcinoma of the cervix. II. To determine and compare the frequency and severity of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 for the regimens administered on this study. SECONDARY OBJECTIVES: I. To estimate and compare the progression-free survival of patients treated by the regimens investigated on this study. II. To estimate and compare the proportion of patients with tumor responses by the regimens investigated on this study. TERTIARY OBJECTIVES: I. To determine whether the addition of bevacizumab to chemotherapy, or the substitution of cisplatin with topotecan improve the health related quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy-Cervix Trial Outcome Index scale (FACT-Cx TOI) and produce favorable toxicity profiles (with a particular focus on peripheral neuropathy as measured by the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity version 4 \[FACT/GOG-Ntx4\] subscale and pain as measured by Brief Pain Inventory \[BPI\] single item). II. To evaluate the impact of age, race, performance status, stage, histology, grade, disease site, prior chemotherapy with primary radiation, and time to recurrence on response rate, progression-free survival and overall survival of patients with metastatic/recurrent/persistent carcinoma of the cervix. III. To determine the prevalence of active smoking in this cohort of recurrent cervical cancer patients. IV. To estimate the extent of tobacco/nicotine dependence in the cohort. V. To determine if smoking is an independent risk factor for progression-free survival and overall survival in this population. VI. To isolate, enumerate and characterize circulating tumor cells (CTC) recovered from blood drawn pre-cycle 1, pre-cycle 2 and pre-cycle 3 using the CTC-chip developed by the Massachusetts General Hospital (MGH) BioMEMS Resource Center and the MGH Cancer Center. VII. To determine the association between CTC counts or characteristics and measures of clinical outcome. VIII. To examine the association between angiogenesis markers in plasma (recovered from blood drawn pre-cycle 1, pre-cycle 2 and pre-cycle 3) and measures of clinical outcome. IX. To evaluate the association between tumor markers of angiogenesis and hypoxia (using archival formalin-fixed and paraffin-embedded tumor tissue) and measures of clinical outcome. X. To evaluate the association between single nucleotide polymorphisms (using deoxyribonucleic acid \[DNA\] extracted from whole blood) and measures of clinical outcome as well as measures of quality of life such as chemotherapy toxicity. XI. To examine the relationship(s) among the various biomarkers. XII. To develop an optimal prognostic model for progression-free survival and overall survival using clinical covariates, smoking status and the various biomarkers. OUTLINE: Patients are randomized to 1 of 4 treatment arms. ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours or 24 hours on day 1 and cisplatin IV on day 1 or 2. ARM II: Patients receive paclitaxel IV over 3 hours or 24 hours on day 1 and cisplatin IV and bevacizumab IV over 30-90 minutes on day 1 or 2. ARM III: Patients receive paclitaxel IV over 3 hours on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3. ARM IV: Patients receive paclitaxel IV over 3 hours and bevacizumab IV over 30-90 minutes on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3. In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
452
Given IV
Given IV
Correlative studies
Given IV
Ancillary studies
Ancillary studies
Given IV
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, United States
Saint Joseph's Hospital and Medical Center
Phoenix, Arizona, United States
Highlands Oncology Group PA - Fayetteville
Fayetteville, Arkansas, United States
Washington Regional Medical Center - Fayetteville
Fayetteville, Arkansas, United States
Overall Survival
The observed length of life from randomization into the study to death or the date of last contact.
Time frame: From entry into the study to death or the date of last contact, assessed up to 5 years
Progression-free Survival
Disease that can be assessed clinically (physical examination) should be evaluated every cycle (every 3 weeks). Disease assessed by imaging modalities (CXR, CT, MRI) should be evaluated every other cycle unless other evidence of a change mandates earlier assessment. Tumor measurements should also be done after the final cycle (if the patient is taken off of study therapy for a reason other than progression) and then every 3 months x 2 years (followed with every 6 months x 3 years) until progression is documented. "Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions assessed radiographically and 50% increase if the only target lesion is a solitary pelvic mass measured by physical exam, or unequivocal progression of a non-target lesion, or the appearance of new lesions", or similar definition as accurate and appropriate.
Time frame: From study entry until disease progression, death or date of last contact, assessed up to 5 years (During treatment: every 3 weeks if by physical exam, every 6 weeks by CXR, CT or MRI. In follow-up: quarterly for 2 years then semi-annually for 3 years)
Tumor Response
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions by CT, MRI or CXR. If the only target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% increase in longest diameter is required; Overall Response (OR) = CR + PR.
Time frame: Every cycle (if assessed by physical exam), every other cycle (if assessed by imaging), after the final cycle, then every 3 months x 2 years, then every 6 months x 3 years up to 5 years.
To Determine and Compare the Frequency and Severity of Adverse Events as Assessed by CTCAE Version 3.0 for the Regimens Administered on This Study.
The number of patients on each arm who have Grade 3 AE or higher toxicity.
Time frame: From date of enrollment until 30 days after treatment completion
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, United States
Roy and Patricia Disney Family Cancer Center
Burbank, California, United States
Mills - Peninsula Hospitals
Burlingame, California, United States
...and 539 more locations