CIRCCa - A Randomized Double Blind Phase II Trial of Carboplatin-Paclitaxel Plus Cediranib Versus Carboplatin-Paclitaxel Plus Placebo in Metastatic/Recurrent Cervical Cancer
CIRCCa - A Randomized Double Blind Phase II Trial of Carboplatin-Paclitaxel Plus Cediranib Versus Carboplatin-Paclitaxel Plus Placebo in Metastatic/Recurrent Cervical Cancer
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.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
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.
DISEASE CHARACTERISTICS:
Histologically confirmed carcinoma of the cervix, including any of the following subtypes:
Must meet one of the following criteria:
Not suitable for potentially curative surgical procedure
Measurable disease in ≥ 1 marker site
No CNS disease, including brain metastases, within the past 6 months
PATIENT CHARACTERISTICS:
ECOG performance status 0-1
Life expectancy > 12 weeks
Hemoglobin ≥ 10 g/dL
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Calculated creatinine clearance ≥ 35 mL/min
No proteinuria > 1+ on dipstick (on 2 consecutive dipsticks not less than 1 week apart), unless urinary protein is < 1.5 g in a 24-hour period
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT or AST ≤ 2.5 times ULN (≤ 5 times ULN if hepatic metastases present)
Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN if hepatic metastases present)
Prothrombin ratio (PTR)/INR ≤ 1.5 OR PTR/INR 2.0-3.0 for patients on stable dose of anticoagulant
Partial thromboplastin time < 1.2 times control
No history of a nervous or psychiatric disorder that would prevent informed consent and compliance
No prior malignancy within the past 5 years, except for successfully treated basal cell skin cancer or in-situ breast cancer
Not pregnant or nursing
Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
No uncontrolled infection, defined as infection that cannot be resolved readily with antibiotics prior to trial entry
No history of significant gastrointestinal impairment, as judged by the Investigator, that would significantly affect the absorption of cediranib maleate
No history of pelvic fistula
No history of inflammatory bowel disease
No sub-acute or acute intestinal obstruction
No significant traumatic injury within the past 4 weeks
No non-healing wound, ulcer, or bone fracture
No active bleeding
No history or evidence of thrombotic or hemorrhagic disorders
No uncontrolled seizures, cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
No significant cardiovascular disease, including any of the following:
Patients with rate-controlled atrial fibrillation are eligible
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:
No concurrent grapefruit juice or St. John wort
London, England W1T 4TJ, United Kingdom