Cediranib, Paclitaxel, and Carboplatin in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

NCT ID: NCT00795340

Last Updated: 2023-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 306 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-04
• Study Completion Date: 2014-01-16

Brief Summary

RATIONALE: Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. It is not yet known whether cediranib is more effective than a placebo when given together with paclitaxel and carboplatin in treating patients with non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying how well cediranib works when given together with paclitaxel and carboplatin in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Detailed Description

OBJECTIVES:

Primary

• To compare overall survival of patients with stage IIIB-IV non-small cell lung cancer treated with cediranib vs placebo administered in combination with paclitaxel and carboplatin.

Secondary

• To compare the progression-free survival of patients treated with these regimens.
• To compare the objective response rates in patients treated with these regimens.
• To estimate time to response and response duration in patients treated with these regimens.
• To evaluate the nature, severity, and frequency of toxicities, including hemorrhage and hemoptysis, in patients treated with these regimens.
• To compare the pharmacokinetics of paclitaxel between the two arms in a subset of enrolled patients
• To compare the quality of life of patients treated with these regimens.
• To determine the incremental cost effectiveness and cost utility ratios for these regimens.
• To correlate the expression of tissue markers (at diagnosis) with outcomes and response in an exploratory fashion OUTLINE: This is a multicenter study. Patients are stratified by gender, center, disease stage (IIIB vs IV), weight loss (< 5% vs 5-10% vs unknown), and prior adjuvant chemotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.
• Arm I: Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1.
• Arm II: Patients receive oral placebo once daily on days 1-21 and paclitaxel and carboplatin as in arm I.

Treatment in both arms repeats every 21 days for 4 to 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, on day 1 of each course, and periodically thereafter.

After completion of study therapy, patients are followed every 12 weeks.

Conditions

Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm I Cediranib

Patients receive oral cediranib once daily on days 1-21 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1.

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

Given IV

cediranib maleate

Intervention Type: DRUG

Given orally

paclitaxel

Intervention Type: DRUG

Given IV

Arm II Placebo

Patients receive oral placebo once daily on days 1-21 and paclitaxel and carboplatin as in arm I.

Group Type: PLACEBO_COMPARATOR

carboplatin

Intervention Type: DRUG

Given IV

paclitaxel

Intervention Type: DRUG

Given IV

placebo

Intervention Type: OTHER

Given orally

Interventions

carboplatin

Given IV

Intervention Type: DRUG

cediranib maleate

Given orally

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

placebo

Given orally

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• No pleural effusion

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine clearance > 50 mL/min
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 2 times ULN (< 5 times ULN if due to liver metastasis)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-method contraception (barrier method for men)
• No other malignancy within the past 5 years, except in situ cancer, basal cell or squamous cell skin cancer, or malignancy cured by definitive prior therapy alone (e.g., surgery) and continuously disease-free for at least 5 years
• Mean QTc with Bazett correction ≤ 480 msec in screening ECG (at least one value must be ≤ 480 msec when measured automatically or manually corrected using Bazett's or Fridericia's correction)
• No history of familial long QT syndrome
• No untreated and/or uncontrolled cardiovascular conditions and/or symptomatic cardiac dysfunction including any of the following:

• Unstable angina
• Congestive heart failure
• Myocardial infarction within the past year
• Cardiac ventricular arrhythmias requiring medication
• History of second or third degree atrioventricular conduction defects
• LVEF > 50% in patients with significant cardiac history, even if controlled
• No resting BP consistently > 150 mm Hg systolic and/or > 100 mm Hg diastolic
• No poorly controlled hypertension
• No history of labile hypertension or poor compliance with anti-hypertensive medication
• No overt bleeding (> 30 mL bleeding/episode) from any site within the past 3 months
• No clinically relevant hemoptysis (> 5 mL fresh blood) within the past 4 weeks

• Flecks of blood in sputum allowed
• No active or uncontrolled infections, or serious illnesses or medical conditions which would not permit the patient to be treated according to the study
• No prior allergic reactions to drugs containing Cremophor EL®
• No inflammatory bowel disease (e.g., Crohn disease or ulcerative colitis)
• No documented weight loss > 10% within the past 3 months

• Patients with weight loss 5-10% or whose weight loss status is unknown are eligible provided serum albumin levels are ≥ 30 g/L
• No peripheral neuropathy > grade 1
• Must be fit for combined modality treatment
• Sufficiently fluent and willing to complete quality-of-life questionnaires

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from all prior therapy
• No prior chemotherapy for metastatic or recurrent disease
• No prior anti-angiogenic therapy (e.g., bevacizumab, cediranib, AZD6474, PTK/ZK, sunitinib malate, or other agents considered angiogenesis inhibitors by NCIC Clinical Trials Group for any indication)

• Prior cox-2 inhibitors in standard doses allowed
• At least 12 months since prior adjuvant chemotherapy for completely resected disease

• Combined chemotherapy/radiotherapy regimens for locally advanced stage IIIB disease not allowed
• At least 21 days since prior radiotherapy
• At least 21 days since prior cetuximab or other monoclonal antibodies
• At least 14 days since prior EGFR inhibitor therapy for adjuvant therapy or metastatic disease (e.g., tyrosine kinase inhibitors, vaccines, or other agents considered by NCIC CTG as acting on the EGFR pathway)
• At least 14 days since prior major surgery
• At least 1 week since prior corticosteroids
• No other concurrent experimental drugs, anticancer treatment, or investigational therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott A. Laurie, MD, FRCPC

Role: STUDY_CHAIR

Ottawa Regional Cancer Centre

Locations

Instituto Nacional de Cancer (INCA)

Rio de Janeiro, , Brazil

Instituto de Cancer Arnaldo Vieira de Carvalho

São Paulo, , Brazil

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

BCCA - Abbotsford Centre

Abbotsford, British Columbia, Canada

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Ottawa Health Research Institute - General Division

Ottawa, Ontario, Canada

Algoma District Cancer Program

Sault Ste. Marie, Ontario, Canada

Niagara Health System

St. Catharines, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Windsor Regional Cancer Centre

Windsor, Ontario, Canada

McGill University - Dept. Oncology

Montreal, Quebec, Canada

University Institute of Cardiology and

Québec, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Countries

Brazil; Canada

References

Laurie SA, Solomon BJ, Seymour L, Ellis PM, Goss GD, Shepherd FA, Boyer MJ, Arnold AM, Clingan P, Laberge F, Fenton D, Hirsh V, Zukin M, Stockler MR, Lee CW, Chen EX, Montenegro A, Ding K, Bradbury PA. Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29. Eur J Cancer. 2014 Mar;50(4):706-12. doi: 10.1016/j.ejca.2013.11.032. Epub 2013 Dec 17.

Reference Type: RESULT

PMID: 24360368 (View on PubMed)

Other Identifiers

CAN-NCIC-BR29

Identifier Type: -

Identifier Source: secondary_id

CDR0000618671

Identifier Type: OTHER

Identifier Source: secondary_id

BR29

Identifier Type: -

Identifier Source: org_study_id