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

Sponsor

University of Glasgow (Other)

Overall Status

Completed

CT.gov ID

NCT01229930

Collaborator

(none)

130

Enrollment

Locations

Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer	Drug: carboplatin Drug: cediranib maleate Drug: paclitaxel Other: laboratory biomarker analysis Other: pharmacological study Procedure: quality-of-life assessment	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

130 participants

Allocation:

Randomized

Masking:

Double

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

Study Start Date :

Jun 1, 2010

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Outcome Measures

Primary Outcome Measures

Overall progression-free survival []

Secondary Outcome Measures

Reduction in plasma VEGFR2 levels from baseline to day 28 []
Response to chemotherapy using RECIST1.1 criteria []
Overall survival []
Toxicity assessed using NCI CTCAE v4.0 []
Quality of life assessed using EORTC QLQ-C30 and CX24 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed carcinoma of the cervix, including any of the following subtypes:
Squamous cell carcinoma
Adenocarcinoma
Adenosquamous cell carcinoma
Must meet one of the following criteria:
Persistent or relapsed inoperable disease after radical radiotherapy within the irradiated pelvis
Relapse after radical hysterectomy (after radical radiotherapy to pelvis, if appropriate)
Extra pelvic metastases
Primary stage IVB disease
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:
Arterial thrombotic event within the past 12 months
Angina within the past 6 months
History of poorly controlled or uncontrolled hypertension or resting BP > 150/100 mm Hg in the presence or absence of a stable regimen of anti-hypertensive therapy within the past 6 months
NYHA class II-IV congestive heart failure
Peripheral vascular disease ≥ grade 3 or cardiac arrhythmia requiring medication
Prolonged QTc (corrected) interval of > 470 ms on ECG or a family history of long QT syndrome
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:
Amiodarone
Clarithromycin
Erythromycin
Simvastatin
Atorvastatin
Lovastatin
Montelukast sodium
Verapamil
Ketoconazole
Miconazole
Indinavir (and other antivirals)
Diltiazem
No concurrent grapefruit juice or St. John wort

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leicester Royal Infirmary	Leicester	England	United Kingdom	LE19 4LF
2	Cancer Research UK and University College London Cancer Trials Centre	London	England	United Kingdom	W1T 4TJ
3	Christie Hospital	Manchester	England	United Kingdom	M20 4BX
4	Royal Marsden - Surrey	Sutton	England	United Kingdom	SM2 5PG
5	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland	United Kingdom	EH4 2XR