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

NCT00795340 | Completed Phase 3 Results DMC

• 3 other identifiers: BR29CAN-NCIC-BR29CDR0000618671
• Study Type: interventional
• Target: 306
• Locations: 2 countries
• Sites: 19

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.

Conditions

Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Medians of survival time, and their confidence intervals.

  at every 3 months visit throughout trial, a median of 13.1 months.

Secondary Outcomes (2)

• Progression-free Survival

  at every 3 months visit throughout trial, a median of 12 months

• Objective Tumor Response as Assessed by RECIST Criteria v1.1.

  Every 6 weeks at the end of every 2 cycles during protocol treatment and every 12 weeks after protocol treatment until progression.

Study Arms (2)

Arm I Cediranib

EXPERIMENTAL

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.

Drug: carboplatin; Drug: cediranib maleate; Drug: paclitaxel

Arm II Placebo

PLACEBO COMPARATOR

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

Drug: carboplatin; Drug: paclitaxel; Other: placebo

Interventions

carboplatin DRUG

Given IV

Arm I Cediranib; Arm II Placebo

cediranib maleate DRUG

Given orally

Arm I Cediranib

paclitaxel DRUG

Given IV

Arm I Cediranib; Arm II Placebo

placebo OTHER

Given orally

Arm II Placebo

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically or cytologically\* confirmed non-small cell carcinoma of the lung * Stage IIIB or IV disease NOTE: \*Diagnosis by sputum cytology alone allowed provided it is confirmed by a second sputum specimen * Measurable disease, defined as at least 1 measurable lesion \> 20 mm by x-ray, ultrasound, or physical exam or ≥ 10 mm (lymph nodes must be ≥ 15 mm in the short axis) by spiral CT scan or physical exam (in the first 260 patients randomized\*\*) * Measurable lesions that are sole sites of disease must be outside a previous radiotherapy field unless disease progression has been documented NOTE: \*\*Measurable or nonmeasurable disease allowed after the first 260 patients * No appreciable cavitation in central thoracic lesions * No untreated brain or meningeal metastases * Patients with treated and radiologic or clinical evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible provided the metastases are asymptomatic and do not require corticosteroids * 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

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 (19)

Instituto Nacional de Cancer (INCA)

Rio de Janeiro, CEP20231-050, Brazil

Location

Instituto de Cancer Arnaldo Vieira de Carvalho

São Paulo, 01224-010, Brazil

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Abbotsford Centre

Abbotsford, British Columbia, V2S 0C2, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, 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

Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

University Institute of Cardiology and

Québec, Quebec, G1V 4G5, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Related Publications (1)

• 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.

  PMID: 24360368 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

Limitations and Caveats

Early termination at phase II part of the trial, leading to small numbers of subjects analyzed, and limited follow up time.

Results Point of Contact

• Title: Dr. Scott Laurie
• Organization: Division of Medical Oncology, the Ottawa Hospital, Ottawa, Ontario, Canada

slaurie@toh.on.ca

1-613-737-7700

Study Officials

• Scott A. Laurie, MD, FRCPC

  Ottawa Regional Cancer Centre

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2008
• First Posted: November 21, 2008
• Study Start: February 4, 2009
• Primary Completion: January 9, 2012
• Study Completion: January 16, 2014
• Last Updated: August 22, 2023
• Results First Posted: December 22, 2015

Record last verified: 2015-06

Data Sharing

• IPD Sharing: Will not share

Locations

BR (2); CA (17)