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

NCT01229930 | Completed Phase 2

• 6 other identifiers: CDR0000687338CRUK-C-2009-01EUDRACT-2009-011542-25ISRCTN-23516549EU-21080ZENECA-CRUK-C-2009-01
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (1)

• Overall progression-free survival

Secondary Outcomes (5)

• 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

Interventions

carboplatin DRUG

cediranib maleate DRUG

paclitaxel DRUG

laboratory biomarker analysis OTHER

pharmacological study OTHER

quality-of-life assessment PROCEDURE

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Glasgow: lead

Study Sites (5)

Leicester Royal Infirmary

Leicester, England, LE19 4LF, United Kingdom

Location

Cancer Research UK and University College London Cancer Trials Centre

London, England, W1T 4TJ, United Kingdom

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

Royal Marsden - Surrey

Sutton, England, SM2 5PG, United Kingdom

Location

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, EH4 2XR, United Kingdom

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Carboplatin; cediranib; Paclitaxel

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• R. Paul Symonds, MD, FRCP, FRCR

  University Hospitals, Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 27, 2010
• First Posted: October 28, 2010
• Study Start: June 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 26, 2013

Record last verified: 2010-10

Locations

GB (5)