Carboplatin and Paclitaxel With or Without Cediranib Maleate in Treating Patients With Metastatic or Recurrent Cervical Cancer That Cannot Be Removed by Surgery
RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether carboplatin and paclitaxel are more effective when given with or without cediranib maleate in treating patients with cervical cancer that cannot be removed by surgery.
PURPOSE: This randomized phase II trial is studying giving carboplatin and paclitaxel together with cediranib maleate to see how well it works compared with giving carboplatin and paclitaxel together with a placebo in treating patients with metastatic or recurrent cervical cancer that cannot be removed by surgery.
Drug: cediranib maleate
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: quality-of-life assessment
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||CIRCCa - A Randomized Double Blind Phase II Trial of Carboplatin-Paclitaxel Plus Cediranib Versus Carboplatin-Paclitaxel Plus Placebo in Metastatic/Recurrent Cervical Cancer|
- Overall progression-free survival [ Designated as safety issue: No ]
- Reduction in plasma VEGFR2 levels from baseline to day 28 [ Designated as safety issue: No ]
- Response to chemotherapy using RECIST1.1 criteria [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Toxicity assessed using NCI CTCAE v4.0 [ Designated as safety issue: Yes ]
- Quality of life assessed using EORTC QLQ-C30 and CX24 [ Designated as safety issue: No ]
|Study Start Date:||June 2010|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
- To provide preliminary evidence regarding whether the addition of cediranib maleate to a combination of carboplatin and paclitaxel will increase the progression-free survival by 50% from 4 to 6 months in patients with metastatic or recurrent, undetectable cervical carcinoma.
- To provide estimates of differences in response, survival, toxicity, quality of life, and pharmacodynamic end-points between the study arms.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive carboplatin IV over 30-60 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive oral placebo once daily.
- Arm II: Patients receive carboplatin and paclitaxel therapy as in Arm I. Patients also receive oral cediranib maleate once daily.
In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete response, partial response, or stable disease following completion of therapy receive cediranib maleate or placebo until evidence of progression or toxicity.
Blood samples may be collected periodically for evaluation of the VEGFR signaling inhibitor cediranib maleate and identification of suitable biomarkers that predict cediranib maleate response. Quality-of-life is assessed by the EORTC QLQ-C30 and QLQ-CX24 cervix subscale questionnaires at baseline and periodically during study and follow up.
After completion of study therapy, patients are followed up every 2 months for 3 years, every 6 months for 2 years, and then annually thereafter.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
|Leicester Royal Infirmary|
|Leicester, England, United Kingdom, LE19 4LF|
|Cancer Research UK and University College London Cancer Trials Centre|
|London, England, United Kingdom, W1T 4TJ|
|Manchester, England, United Kingdom, M20 4BX|
|Royal Marsden - Surrey|
|Sutton, England, United Kingdom, SM2 5PG|
|Edinburgh Cancer Centre at Western General Hospital|
|Edinburgh, Scotland, United Kingdom, EH4 2XR|
|Principal Investigator:||R. Paul Symonds, MD, FRCP, FRCR||University Hospitals, Leicester|