Carboplatin and Paclitaxel With or Without Cediranib Maleate in Treating Patients With Metastatic or Recurrent Cervical Cancer That Cannot Be Removed by Surgery

NCT ID: NCT01229930

Last Updated: 2013-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2012-12-31

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

• 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.

Secondary

• 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.

Conditions

Cervical Cancer

Keywords

cervical adenocarcinoma; cervical adenosquamous cell carcinoma; cervical squamous cell carcinoma; recurrent cervical cancer; stage IVB cervical cancer; stage IVA cervical cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

carboplatin

Intervention Type: DRUG

cediranib maleate

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

quality-of-life assessment

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Not requiring intravenous nutritional support
• No preexisting sensory or motor neuropathy ≥ grade 2
• No history or clinical suspicion of spinal cord compression
• No known hypersensitivity to carboplatin or paclitaxel
• No evidence of any other disease, metabolic dysfunction, physical examination finding, or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No unresolved toxicity ≥ CTC grade 2 from prior systemic anti-cancer therapy, except hematological toxicity or alopecia
• No prior chemotherapy, except cisplatin administered along with radiotherapy as primary treatment
• No major surgery within 28 days or anticipated while on study
• More than 2 weeks since prior and no concurrent potent inhibitors of CYP3A4 and 2C8, including any of the following:

• Amiodarone
• Clarithromycin
• Erythromycin
• Simvastatin
• Atorvastatin
• Lovastatin
• Montelukast sodium
• Verapamil
• Ketoconazole
• Miconazole
• Indinavir (and other antivirals)
• Diltiazem
• No concurrent grapefruit juice or St. John wort

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Glasgow

OTHER

Sponsor Role: lead

Principal Investigators

R. Paul Symonds, MD, FRCP, FRCR

Role: PRINCIPAL_INVESTIGATOR

University Hospitals, Leicester

Locations

Leicester Royal Infirmary

Leicester, England, United Kingdom

Cancer Research UK and University College London Cancer Trials Centre

London, England, United Kingdom

Christie Hospital

Manchester, England, United Kingdom

Royal Marsden - Surrey

Sutton, England, United Kingdom

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, United Kingdom

Countries

United Kingdom

Other Identifiers

CRUK-C-2009-01

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2009-011542-25

Identifier Type: -

Identifier Source: secondary_id

ISRCTN-23516549

Identifier Type: -

Identifier Source: secondary_id

EU-21080

Identifier Type: -

Identifier Source: secondary_id

ZENECA-CRUK-C-2009-01

Identifier Type: -

Identifier Source: secondary_id

CDR0000687338

Identifier Type: -

Identifier Source: org_study_id