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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00245154
• Other study ID #: BR24
• Secondary ID: CAN-NCIC-BR24ZEN
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: November 3, 2005
• Est. completion date: January 10, 2013

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 296
• Est. completion date: January 10, 2013
• Est. primary completion date: July 4, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• carboplatin
Given IV
• cediranib maleate
Given orally
• paclitaxel
Given IV

Other:
• placebo
Given orally

Locations

Country	Name	City	State
Argentina	Compleso Medico de la Policia Federal Argentina	Buenos Aires
Argentina	Hospital Universitario Austral	Buenos Aires
Argentina	Instituto Alexander Fleming	Buenos Aires
Australia	Alfred Hospital	Melbourne
Brazil	Instituto Nacional de Cancer (INCA)	Rio de Janeiro
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	Ottawa Health Research Institute - General Division	Ottawa	Ontario
Canada	University Institute of Cardiology and	Quebec
Canada	Algoma District Cancer Program	Sault Ste. Marie	Ontario
Canada	Niagara Health System	St. Catharines	Ontario
Canada	Northeast Cancer Center Health Sciences	Sudbury	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Romania	Oncology Institute Bucharest	Bucharest
Romania	Oncological Institute "Ion Chiricuta"	Cluj-Napoca
Romania	Clinical County Hospital of Sibiu	Sibiu
Singapore	National University Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Countries where clinical trial is conducted

Argentina,  Australia,  Brazil,  Canada,  Romania,  Singapore, 

References & 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.

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 pac — View Citation

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 kin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		3 years
Secondary	Toxicity		3 years
Secondary	Quality of Life		3 years
Secondary	Overall survival		3 years
Secondary	Correlative Studies		3 years