Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Advanced, Metastatic, or Recurrent Non-Small Cell Lung Cancer - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborators:	National Cancer Institute (NCI) Cancer and Leukemia Group B
Information provided by:	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00021060

Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining chemotherapy with a monoclonal antibody may kill more tumor cells.

PURPOSE: This randomized phase II/III trial is to see if combination chemotherapy works better with or without bevacizumab in treating patients who have advanced, metastatic, or recurrent non-small cell lung cancer.

Condition	Intervention	Phase
Lung Cancer	Biological: bevacizumab Drug: carboplatin Drug: paclitaxel	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	Randomized Phase II/III Trial of Paclitaxel Plus Carboplatin With or Without Bevacizumab (NSC #704865) in Patients With Advanced Nonsquamous NSCLC

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Paclitaxel Carboplatin Bevacizumab

U.S. FDA Resources

Further study details as provided by Eastern Cooperative Oncology Group:

Study Start Date:	July 2001
Primary Completion Date:	September 2006 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Compare the toxicity of paclitaxel and carboplatin with or without bevacizumab in patients with advanced, metastatic, or recurrent non-squamous cell non-small cell lung cancer.
Compare the survival of patients treated with these regimens.
Compare the response rates and time to progression in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to measurable disease (yes vs no), prior radiotherapy (yes vs no), weight loss (less than 5% vs 5% or more), and disease stage (IIIB vs IV vs recurrent). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 15-30 minutes on day 1.
Arm II: Patients receive paclitaxel and carboplatin as in arm I followed by bevacizumab IV over 30-90 minutes on day 1.

Treatment in both arms repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of 6 courses, patients in arm II with stable or responding disease continue to receive bevacizumab only. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 842 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
- Stage IIIB with malignant pleural effusion, stage IV, or recurrent
- Measurable or nonmeasurable disease
No squamous cell NSCLC
No known CNS metastases by head CT scan or MRI within the past 4 weeks

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-1

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
No prior thrombotic or hemorrhagic disorders

Hepatic:

Bilirubin no greater than 1.5 mg/dL
Transaminases no greater than 5 times upper limit of normal (ULN)
PTT normal
INR no greater than 1.5

Renal:

Creatinine no greater than 1.5 times ULN
Urine protein less than 1+ (i.e., trace or 0 by dipstick or urinalysis) OR
24-hour urine protein less than 500 mg

Cardiovascular:

No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
Concurrent hypertension allowed provided well-controlled on a stable regimen of anti-hypertensive therapy

Pulmonary:

No history of gross hemoptysis (½ teaspoon of bright red blood or more)

Other:

No ongoing or active infection
No serious non-healing wound ulcer
No bone fracture
No psychiatric illness or social situation that would preclude study compliance
No other concurrent comorbidities that would preclude study participation
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 3 weeks since prior immunotherapy and recovered

Chemotherapy:

No prior systemic chemotherapy

Endocrine therapy:

At least 3 weeks since prior hormonal therapy and recovered

Radiotherapy:

At least 3 weeks since prior radiotherapy and recovered

Surgery:

At least 3 weeks since prior major surgery

Other:

No concurrent therapeutic anticoagulation
No concurrent chronic daily aspirin (greater than 325 mg/day)
No concurrent non-steroidal anti-inflammatory agents known to inhibit platelet function (arm II only)
No concurrent dipyridamole, ticlopidine, clopidogrel, and/or cilostazol

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00021060

Show 78 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Cancer and Leukemia Group B

Investigators

Study Chair:	Alan B. Sandler, MD	Vanderbilt-Ingram Cancer Center
Study Chair:	Michael C. Perry, MD	Ellis Fischel Cancer Center at University of Missouri - Columbia

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Dowlati A, Gray R, Sandler AB, Schiller JH, Johnson DH. Cell Adhesion Molecules, Vascular Endothelial Growth Factor, and Basic Fibroblast Growth Factor in Patients with Non-Small Cell Lung Cancer Treated with Chemotherapy with or without Bevacizumab--an Eastern Cooperative Oncology Group Study. Clin Cancer Res. 2008 Mar 1;14(5):1407-12.

Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008 Jan 1;26(1):60-5.

Somer RA, Sherman E, Langer CJ. Restrictive eligibility limits access to newer therapies in non-small-cell lung cancer: the implications of Eastern Cooperative Oncology Group 4599. Clin Lung Cancer. 2008 Mar;9(2):102-5.

Cohen MH, Gootenberg J, Keegan P, Pazdur R. FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. Oncologist. 2007 Jun;12(6):713-8.

Ramalingam SS, Dahlberg SE, Langer CJ, et al.: Outcomes for elderly advanced stage non-small cell lung cancer (NSCLC) patients (pts) treated with bevacizumab (B) in combination with carboplatin (C) and paclitaxel (P): analysis of Eastern Cooperative Oncology Group (ECOG) 4599 study. [Abstract] J Clin Oncol 25 (Suppl 18): A-7535, 393s, 2007.

Brahmer JR, Gray R, Schiller JH, et al.: ECOG 4599 phase III trial of carboplatin and paclitaxel ±bevacizumab: subset analysis of survival by gender. [Abstract] J Clin Oncol 24 (Suppl 18): A-7036, 373s, 2006.

Dowlati A, Gray R, Johnson DH, et al.: Prospective correlative assessment of biomarkers in E4599 randomized phase II/III trial of carboplatin and paclitaxel ± bevacizumab in advanced non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 24 (Suppl 18): A-7027, 370s, 2006.

Sandler AB, Johnson DH, Brahmer J, et al.: Retrospective study of clinical and radiographic risk factors associated with early onset, severe pulmonary hemorrhage in bevacizumab-treated patients with advanced non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 24 (Suppl 18): A-7068, 381s, 2006.

Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50.

Sandler AB, Gray R, Brahmer J, et al.: Randomized phase II/III trial of paclitaxel (P) plus carboplatin (C) with or without bevacizumab (NSC # 704865) in patients with advanced non-squamous non-small cell lung cancer (NSCLC): an Eastern Cooperative Oncology Group (ECOG) Trial - E4599. [Abstract] J Clin Oncol 23 (Suppl 16): A-LBA4, 2s, 2005.

Tyagi P. Bevacizumab, when added to paclitaxel/carboplatin, prolongs survival in previously untreated patients with advanced non-small-cell lung cancer: preliminary results from the ECOG 4599 trial. Clin Lung Cancer. 2005 Mar;6(5):276-8. No abstract available.

Sandler A: Bevacizumab in non small cell lung cancer. Clin Cancer Res 13 (15): 4613s-6s, 2007.

Dornbusch D, Allegra C, Willey J, Andrews M, Leff R, Epstein J, Jones J, Lokey L, Green MR. How do U.S. medical oncologists learn and apply new clinical trials information from press releases in nonmedical media? A case study based on ECOG 4599. Oncologist. 2006 Jan;11(1):31-8.

Gray R, Giantonio BJ, O'Dwyer PJ, et al.: The safety of adding angiogenesis inhibition into treatment for colorectal, breast, and lung cancer: the Eastern Cooperative Oncology Group's (ECOG) experience with bevacizumab (anti-VEGF). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-825, 2003.

Responsible Party:	Group Chair, Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00021060 History of Changes
Other Study ID Numbers:	CDR0000068744, E4599, CALGB-E4599
Study First Received:	July 11, 2001
Last Updated:	January 26, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:

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

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Bevacizumab
Carboplatin
Paclitaxel

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012