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

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00245154

Collaborator

(none)

296

Enrollment

Locations

Arms

88.1

Actual Duration (Months)

14.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: carboplatin Drug: cediranib maleate Drug: paclitaxel Other: placebo	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

296 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, 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

Actual Study Start Date :

Sep 7, 2005

Actual Primary Completion Date :

Jul 4, 2008

Actual Study Completion Date :

Jan 10, 2013

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Progression-free survival [3 years]

Secondary Outcome Measures

Toxicity [3 years]
Quality of Life [3 years]
Overall survival [3 years]
Correlative Studies [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Instituto Alexander Fleming	Buenos Aires		Argentina	1426
2	Compleso Medico de la Policia Federal Argentina	Buenos Aires		Argentina	1437
3	Hospital Universitario Austral	Buenos Aires		Argentina	B1629AHJ
4	Alfred Hospital	Melbourne		Australia	3004
5	Instituto Nacional de Cancer (INCA)	Rio de Janeiro		Brazil	CEP20231-050
6	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
7	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
8	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
9	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
10	Ottawa Health Research Institute - General Division	Ottawa	Ontario	Canada	K1H 8L6
11	Algoma District Cancer Program	Sault Ste. Marie	Ontario	Canada	P6B 0A8
12	Niagara Health System	St. Catharines	Ontario	Canada	L2R 7C6
13	Northeast Cancer Center Health Sciences	Sudbury	Ontario	Canada	P3E 5J1
14	Mount Sinai Hospital	Toronto	Ontario	Canada	M5G 1X5
15	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
16	University Institute of Cardiology and	Quebec		Canada	G1V 4G5
17	Oncology Institute Bucharest	Bucharest		Romania
18	Oncological Institute "Ion Chiricuta"	Cluj-Napoca		Romania	3400
19	Clinical County Hospital of Sibiu	Sibiu		Romania	2400
20	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