Paclitaxel + Carboplatin With/Out Cediranib Maleate in Stage III or Stage IV Non-Small Cell Lung Cancer

NCT00245154 | Completed Phase 2 DMC

• 7 other identifiers: BR24CAN-NCIC-BR24ZENECA-CAN-NCIC-BR24FHCRC-6107UWCC-UW 6107UWCC- 06-2707-H/BCDR0000450850
• Study Type: interventional
• Target: 296
• Locations: 6 countries
• Sites: 20

Brief Summary

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.

Conditions

Lung Cancer

Keywords

stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  3 years

Secondary Outcomes (4)

• Toxicity

  3 years

• Quality of Life

  3 years

• Overall survival

  3 years

• Correlative Studies

  3 years

Study Arms (2)

Arm I

EXPERIMENTAL

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; Drug: cediranib maleate; Drug: paclitaxel

Arm II

ACTIVE COMPARATOR

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; Drug: paclitaxel; Other: placebo

Interventions

carboplatin DRUG

Given IV

Arm I; Arm II

cediranib maleate DRUG

Given orally

Arm I

paclitaxel DRUG

Given IV

Arm I; Arm II

placebo OTHER

Given orally

Arm II

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (20)

Instituto Alexander Fleming

Buenos Aires, 1426, Argentina

Location

Compleso Medico de la Policia Federal Argentina

Buenos Aires, 1437, Argentina

Location

Hospital Universitario Austral

Buenos Aires, B1629AHJ, Argentina

Location

Alfred Hospital

Melbourne, 3004, Australia

Location

Instituto Nacional de Cancer (INCA)

Rio de Janeiro, CEP20231-050, Brazil

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Northeast Cancer Center Health Sciences

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Ottawa Health Research Institute - General Division

Ottawa, Ontario, K1H 8L6, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Niagara Health System

St. Catharines, Ontario, L2R 7C6, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

University Institute of Cardiology and

Québec, Quebec, G1V 4G5, Canada

Location

Oncology Institute Bucharest

Bucharest, Romania

Location

Oncological Institute "Ion Chiricuta"

Cluj-Napoca, 3400, Romania

Location

Clinical County Hospital of Sibiu

Sibiu, 2400, Romania

Location

National University Hospital

Singapore, 119074, Singapore

Location

Related Publications (3)

• Bradbury PA, Twumasi-Ankrah P, Ding K, et al.: The impact of brain metastases on overall survival (OS) in National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) clinical trials (CT) in advanced non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 27 (Suppl 15): A-8075, 2009.

  BACKGROUND

• Laurie SA, Gauthier I, Arnold A, Shepherd FA, Ellis PM, Chen E, Goss G, Powers J, Walsh W, Tu D, Robertson J, Puchalski TA, Seymour L. Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 2008 Apr 10;26(11):1871-8. doi: 10.1200/JCO.2007.14.4741.

  PMID: 18398152 RESULT

• Goss GD, Arnold A, Shepherd FA, Dediu M, Ciuleanu TE, Fenton D, Zukin M, Walde D, Laberge F, Vincent MD, Ellis PM, Laurie SA, Ding K, Frymire E, Gauthier I, Leighl NB, Ho C, Noble J, Lee CW, Seymour L. Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC clinical trials group BR24 study. J Clin Oncol. 2010 Jan 1;28(1):49-55. doi: 10.1200/JCO.2009.22.9427. Epub 2009 Nov 16.

  PMID: 19917841 RESULT

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Carboplatin; cediranib; Paclitaxel

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Glenwood D. Goss, MD, BCh, FCP, FRCPC

  Ottawa Regional Cancer Centre

  STUDY CHAIR

• Scott A. Laurie, MD, FRCPC

  Ottawa Regional Cancer Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2005
• First Posted: October 27, 2005
• Study Start: November 3, 2005
• Primary Completion: July 4, 2008
• Study Completion: January 10, 2013
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

AR (3); BR (1); AU (1); CA (11); SG (1); RO (3)