Trials / Completed

CompletedNCT00803062

Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab in Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer

A Randomized Phase III Trial of Cisplatin Plus Paclitaxel With and Without NCI-Supplied Bevacizumab (NSC #704865) Versus the Non-platinum Doublet, Topotecan Plus Paclitaxel, With and Without NCI-Supplied Bevacizumab, in Stage IVB, Recurrent or Persistent Carcinoma of the Cervix

Status: Completed
Phase: Phase 3
Study type: Interventional
Enrollment: 452 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: Female
Age: 18 Years
Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Bevacizumab	Given IV
DRUG	Cisplatin	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Paclitaxel	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Topotecan Hydrochloride	Given IV

Timeline

Start date: 2009-04-01
Primary completion: 2013-02-01
Completion: 2013-02-01
First posted: 2008-12-05
Last updated: 2019-07-23
Results posted: 2016-05-24

Locations

549 sites across 2 countries: United States, Spain

Source: ClinicalTrials.gov record NCT00803062. Inclusion in this directory is not an endorsement.