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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01229930
First received: October 27, 2010
Last updated: August 23, 2013
Last verified: October 2010
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 130
Study Start Date: June 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01229930

Locations
United Kingdom
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
Christie Hospital
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
Sponsors and Collaborators
University of Glasgow
Investigators
Principal Investigator: R. Paul Symonds, MD, FRCP, FRCR University Hospitals, Leicester
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01229930     History of Changes
Other Study ID Numbers: CDR0000687338, CRUK-C-2009-01, EUDRACT-2009-011542-25, ISRCTN-23516549, EU-21080, ZENECA-CRUK-C-2009-01
Study First Received: October 27, 2010
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
cervical adenocarcinoma
cervical adenosquamous cell carcinoma
cervical squamous cell carcinoma
recurrent cervical cancer
stage IVB cervical cancer
stage IVA cervical cancer

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Maleic acid
Cediranib
Carboplatin
Paclitaxel
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014