Paclitaxel and Carboplatin With or Without Cediranib Maleate in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00245154
First received: October 25, 2005
Last updated: January 10, 2013
Last verified: November 2012
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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. Giving paclitaxel and carboplatin together with AZD2171 may kill more tumor cells. It is not yet known whether giving paclitaxel and carboplatin together with AZD2171 is more effective than giving paclitaxel and carboplatin together with a placebo in treating non-small cell lung cancer.

PURPOSE: This randomized phase II/III trial is studying how well giving paclitaxel and carboplatin together with cediranib maleate works and compares it to giving paclitaxel and carboplatin together with placebo in treating patients with stage III or stage IV non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Drug: carboplatin
Drug: cediranib maleate
Drug: paclitaxel
Other: placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II/III Double Blind Randomized Trial of AZD2171 Versus Placebo in Patients Receiving Paclitaxel/Carboplatin Chemotherapy for the Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Quality of Life [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Correlative Studies [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 296
Study Start Date: September 2005
Study Completion Date: January 2013
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral cediranib maleate once daily in the absence of disease progression or unacceptable toxicity. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment with paclitaxel and carboplatin repeats every 21 days for 6-8 courses in the absence of disease progression or unacceptable toxicity.
Drug: carboplatin
Given IV
Drug: cediranib maleate
Given orally
Drug: paclitaxel
Given IV
Active Comparator: Arm II
Patients receive oral placebo once daily in the absence of disease progression or unacceptable toxicity. Patients also receive paclitaxel and carboplatin as in arm I.
Drug: carboplatin
Given IV
Drug: paclitaxel
Given IV
Other: placebo
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • Compare the progression-free survival of patients with stage IIIB or IV non-small cell lung cancer treated with paclitaxel and carboplatin in combination with either cediranib maleate or a placebo.
  • Determine the pharmacogenomics and pharmacodynamic aspects of these regimens in these patients. (Phase II)
  • Compare the overall survival of patients treated with these regimens. (Phase III)

Secondary

  • Compare objective tumor response rates in patients treated with these regimens.
  • Determine the time to response and response duration in patients treated with these regimens. (Phase III)
  • Determine the nature, severity, and frequency of the toxic effects of these regimens, including hemorrhage and hemoptysis, in these patients.
  • Correlate the expression of tissue markers (at diagnosis) with outcomes and response in patients treated with these regimens. (Phase III)
  • Compare quality of life of patients treated with these regimens. (Phase III)

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to gender, participating center, disease stage (IIIB vs IV), weight loss (≥ 5% vs < 5%), and prior adjuvant chemotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral cediranib maleate once daily in the absence of disease progression or unacceptable toxicity. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment with paclitaxel and carboplatin repeats every 21 days for 6-8 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral placebo once daily in the absence of disease progression or unacceptable toxicity. Patients also receive paclitaxel and carboplatin as in arm I.

Quality of life is assessed at baseline, before each treatment course, after completion of study treatment, and every 3 months thereafter.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 750 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), meeting 1 of the following stage criteria:

    • Stage IIIB disease

      • Patients without pleural effusion who are not candidates for combined modality treatment OR who were treated at centers where combined modality treatment is not considered standard treatment are eligible
    • Stage IV disease
  • Measurable disease (phase II)

    • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by x-ray, ultrasound, physical exam, or conventional CT scan OR ≥ 10 mm by spiral CT scan
    • Measurable lesions must be outside a previous radiotherapy field if they are the sole site of disease, unless disease progression has been documented
    • No significant central thoracic lesion with any appreciable cavitation
  • Measurable or nonmeasurable disease (phase III)
  • No necrotic or hemorrhagic tumor or metastases
  • No untreated brain or meningeal metastases

    • CT scans are not required to rule out disease unless there is clinical suspicion of CNS disease
    • Patients with previously treated stable brain metastases (by radiography or clinical exam) are eligible provided they are asymptomatic and do not require corticosteroids

PATIENT CHARACTERISTICS:

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • No overt bleeding (i.e., ≥ 30 mL/episode) within the past 3 months

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 2 times ULN (< 5 times ULN if liver metastases are present)

Renal

  • Creatinine clearance ≥ 50 mL/min
  • Proteinuria ≤ grade 1

Cardiovascular

  • Mean QTc ≤ 470 msec (with Bazett's correction) by ECG
  • No unstable angina
  • No congestive heart failure
  • No myocardial infarction within the past year
  • No cardiac ventricular arrhythmias requiring medication
  • No history of 2nd- or 3rd-degree atrioventricular conduction defects
  • No untreated or uncontrolled cardiovascular condition
  • No symptomatic cardiac dysfunction
  • No uncontrolled hypertension (i.e., resting blood pressure ≥ 150/100 mm Hg despite antihypertensive therapy)
  • No history of labile hypertension
  • No history of poor compliance with antihypertensive medication
  • No history of familial long-QT syndrome

Pulmonary

  • No clinically relevant hemoptysis (i.e., ≥ 5 mL fresh blood) within the past 4 weeks

    • Flecks of blood only in sputum allowed

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective (double method for females; barrier method for males) contraception
  • Able and willing to participate in the quality of life assessment
  • No peripheral neuropathy > grade 1
  • No prior allergic reaction to drugs containing Cremophor EL®
  • No active or uncontrolled infection
  • No serious illness or medical condition which would preclude study compliance
  • No inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis)
  • No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or in situ cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • At least 14 days since prior epidermal growth factor receptor-inhibitor therapy (e.g., tyrosine kinase inhibitor, monoclonal antibodies, vaccines, or other agents)
  • No prior antiangiogenesis therapy, including any of the following:

    • Bevacizumab
    • Cediranib maleate
    • AZD6474
    • PTK787/ZK222584 (PTK/ZK)
    • Sunitinib malate
  • Concurrent epoetin alfa allowed

Chemotherapy

  • At least 12 months since prior adjuvant chemotherapy

    • Combined chemotherapy and radiotherapy regimens for locally advanced stage IIIB disease is not considered adjuvant therapy and is not allowed
  • No prior chemotherapy for metastatic or recurrent NSCLC

Endocrine therapy

  • See Disease Characteristics
  • At least 1 week since prior steroids

Radiotherapy

  • See Disease Characteristics
  • At least 21 days since prior radiotherapy except for low-dose non-myelosuppressive radiotherapy with approval
  • Concurrent palliative radiotherapy allowed with approval

Surgery

  • At least 14 days since prior major surgery

Other

  • Recovered from prior therapy
  • Prior treatment with cyclooxygenase-2 inhibitors allowed
  • Concurrent prophylactic anticoagulation (e.g., warfarin) allowed provided requirements for INR are met
  • No potent inhibitors of CYP3A4 and 2C8, including any of the following drugs:

    • Amiodarone hydrochloride
    • Clarithromycin
    • Citalopram hydrobromide
    • Erythromycin
    • Omeprazole
    • Simvastatin
    • Atorvastatin
    • Lovastatin
    • Montelukast sodium
    • Verapamil hydrochloride
    • Ketoconazole
    • Miconazole
    • Indinovir and other antivrails
    • Diltiazem
  • No other concurrent experimental drug or anticancer therapy
  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: NCT00245154

Locations
Argentina
Compleso Medico de la Policia Federal Argentina
Buenos Aires, Argentina, 1437
Hospital Universitario Austral
Buenos Aires, Argentina, B1629AHJ
Instituto Alexander Fleming
Buenos Aires, Argentina, 1426
Australia
Alfred Hospital
Melbourne, Australia, 3004
Brazil
Instituto Nacional de Cancer (INCA)
Rio de Janeiro, Brazil, CEP20231-050
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Ottawa Health Research Institute - General Division
Ottawa, Ontario, Canada, K1H 8L6
Algoma District Cancer Program
Sault Ste. Marie, Ontario, Canada, P6B 0A8
Niagara Health System
St. Catharines, Ontario, Canada, L2R 7C6
Northeast Cancer Center Health Sciences
Sudbury, Ontario, Canada, P3E 5J1
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
Canada
University Institute of Cardiology and
Quebec, Canada, G1V 4G5
Romania
Oncology Institute Bucharest
Bucharest, Romania
Oncological Institute "Ion Chiricuta"
Cluj-Napoca, Romania, 3400
Clinical County Hospital of Sibiu
Sibiu, Romania, 2400
Singapore
National University Hospital
Singapore, Singapore, 119074
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Glenwood D. Goss, MD, BCh, FCP, FRCPC Ottawa Regional Cancer Centre
Study Chair: Scott A. Laurie, MD, FRCPC Ottawa Regional Cancer Centre
  More Information

Additional Information:
Publications:
Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00245154     History of Changes
Other Study ID Numbers: BR24, CAN-NCIC-BR24, ZENECA-CAN-NCIC-BR24, FHCRC-6107, UWCC-UW 6107, UWCC- 06-2707-H/B, CDR0000450850
Study First Received: October 25, 2005
Last Updated: January 10, 2013
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Cediranib
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014