A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-small Cell Lung Cancer - Full Text View

Purpose

The purpose of this study is to determine the safety, tolerability and efficacy of combretastatin A4 phosphate (CA4P), also known as fosbretabulin, in combination with bevacizumab (Avastin), carboplatin and paclitaxel in patients with chemotherapy naïve non-small cell lung cancer (NSCLC). This is a randomized parallel arm study. All participants will receive carboplatin, paclitaxel and bevacizumab, and half will additionally receive CA4P. Patients who complete the first 6 cycles of therapy and have not experienced disease progression will receive maintenance therapy with bevacizumab alone or with bevacizumab plus CA4P.

The rationale for this study is the potential additive or synergistic actions of vascular disrupting agents like CA4P with anti-angiogenic agents like bevacizumab.

Condition	Intervention	Phase
Tumors	Drug: CA4P Drug: Carboplatin Drug: Bevacizumab Drug: Paclitaxel	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Study to Assess the Safety and Efficacy of Carboplatin, Paclitaxel and Bevacizumab ± Combretastatin A4 Phosphate (CA4P) Followed by Bevacizumab ± CA4P in Subjects With Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:

MedlinePlus related topics: CT Scans Cancer Lung Cancer Nuclear Scans

Drug Information available for: Paclitaxel Carboplatin Bevacizumab

U.S. FDA Resources

Further study details as provided by OXiGENE:

Primary Outcome Measures:

Safety and tolerability of the combination therapy assessed by analysis of adverse events, physical examination, blood tests, ECGs [ Time Frame: Six 21-day cycles ] [ Designated as safety issue: Yes ]
Progression-free survival as determined from tumor imaging by CT scan [ Time Frame: Six 21-day cycles ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Tumor response rate as determined from tumor imaging by CT scan [ Time Frame: Six 21-day cycles ] [ Designated as safety issue: Yes ]
Overall Survival [ Time Frame: Until death ] [ Designated as safety issue: Yes ]

Enrollment:	63
Study Start Date:	March 2008
Study Completion Date:	October 2011
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm 1: Chemotherapy+ bevacizumab Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) administered intravenously Day 1 every 3 weeks for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevicizumab alone on Day 1 every 3 weeks until progression or until 12 months from randomization.	Drug: Carboplatin Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles. Other Name: Paraplatin Drug: Bevacizumab Bevacizumab (15 mg/kg) on Day 1 of each 21 day cycle for 6 cycles. Other Name: Avastin Drug: Paclitaxel Paclitaxel 20 mg/m sq will be administered on Day 1 of six 21-day cycles Other Name: Taxol
Experimental: Arm 2: Comparator regimen + CA4P Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg),administered intravenously Day 1 with and CA4P (60 mg/m2) on Days 7, 14, and 21 every 3 weeks for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab on Day 1 and CA4P on Days 1, 7 and 14 every 3 weeks until progression or until 12 months from randomization.	Drug: CA4P Arm 2 only: CA4P(60 mg/meter sq) on Days 7,14 and 21 for 6 cycles. Other Names: fosbretabulin combretastatin Zybrestat Drug: Carboplatin Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles. Other Name: Paraplatin Drug: Bevacizumab Bevacizumab (15 mg/kg) on Day 1 of each 21 day cycle for 6 cycles. Other Name: Avastin Drug: Paclitaxel Paclitaxel 20 mg/m sq will be administered on Day 1 of six 21-day cycles Other Name: Taxol

Arms

Assigned Interventions

Active Comparator: Arm 1: Chemotherapy+ bevacizumab

Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) administered intravenously Day 1 every 3 weeks for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevicizumab alone on Day 1 every 3 weeks until progression or until 12 months from randomization.

Drug: Carboplatin

Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.

Other Name: Paraplatin

Drug: Bevacizumab

Bevacizumab (15 mg/kg) on Day 1 of each 21 day cycle for 6 cycles.

Other Name: Avastin

Drug: Paclitaxel

Paclitaxel 20 mg/m sq will be administered on Day 1 of six 21-day cycles

Other Name: Taxol

Experimental: Arm 2: Comparator regimen + CA4P

Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg),administered intravenously Day 1 with and CA4P (60 mg/m2) on Days 7, 14, and 21 every 3 weeks for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab on Day 1 and CA4P on Days 1, 7 and 14 every 3 weeks until progression or until 12 months from randomization.

Drug: CA4P

Arm 2 only: CA4P(60 mg/meter sq) on Days 7,14 and 21 for 6 cycles.

Other Names:

fosbretabulin
combretastatin
Zybrestat

Drug: Carboplatin

Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.

Other Name: Paraplatin

Drug: Bevacizumab

Bevacizumab (15 mg/kg) on Day 1 of each 21 day cycle for 6 cycles.

Other Name: Avastin

Drug: Paclitaxel

Paclitaxel 20 mg/m sq will be administered on Day 1 of six 21-day cycles

Other Name: Taxol

Detailed Description:

Lung cancer has become the leading cause of cancer death in both men and women in the US and Europe, accounting for 29% of all cancer deaths. Non-Small Cell Lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases. Currently, no curative treatment is available for advanced stages of the disease (stages III and IV), which comprise the majority of cases. Treatment with the combination of carboplatin and paclitaxel has been shown to be effective and well tolerated in advanced stage NSCLC. Targeted therapies, such as bevacizumab, often act synergistically with chemotherapy. Bevacizumab inhibits VEGF, necessary for endothelial cell proliferation and new blood vessel formation. CA4P targets existing abnormal vasculature of tumors, impeding tumor blood flow and leading to extensive tumor cell death as a consequence of oxygen and nutrient deprivation.

This study will compare the effect of CA4P when combined with chemotherapy and bevacizumab on progression free survival (PFS) to PFS after chemotherapy and bevacizumab alone.

Eligibility

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

Criteria

Inclusion Criteria:

Pathologically confirmed Stage IIIB NSCLC with malignant pleural effusion, or Stage IV disease
Measurable disease on CT scan (by the RECIST criteria)
Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1 (which means able to independently care for self and to perform light work) .
Adequate blood counts
Adequate liver and kidney function
Subjects or their legal representatives must be able to read, understand and provide written informed consent to participate in the trial.

Exclusion Criteria:

Predominant Squamous Cell NSCLC histology.
History of treatment for NSCLC with chemotherapy, biological therapy, immunotherapy (surgery or radiation therapy are accepted)
Brain (CNS) metastasis by head CT scan or MRI
Subjects with history of prior malignancy except for curatively treated basal cell carcinoma of the skin; cervical intra-epithelial neoplasia; or localized prostate cancer with a current prostate specific antigen (PSA) of < 4.0 mg/dL. Subjects with other curatively treated malignancies who have no evidence of metastatic disease and >2 year disease free interval may be entered after discussion with the Medical Monitor.
History of bleeding disorders, particularly coughing up ≥ ½ teaspoon bright red blood during the last 3 months
Certain cardiac disorders such as recent myocardial infarction (MI), severe congestive heart failure, certain types of abnormal cardiac rhythm
Uncontrolled high blood pressure despite medications
Uncontrolled, clinically significant active infection.
Known HIV
Known hypersensitivity to any of the components of CA4P, paclitaxel, carboplatin, bevacizumab, or radiologic contrast dyes.

Details of the above and additional inclusion and exclusion criteria can be discussed with an investigator.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00653939

Locations

United States, California
Southbay Oncology Hematology
Campbell, California, United States, 95008
Pacific Coast Hematology and Oncology Medical Group
Fountain Valley, California, United States, 92708
UCLA Division of Hematology and Oncology
Los Angeles, California, United States, 90095
Bay Area Cancer Research Group, LLC
Pleasant Hill, California, United States, 94523
United States, Kentucky
Kentuckiana Cancer Institute
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Lahey Clinic Medical Center
Burlington, Massachusetts, United States, 01805
United States, New Jersey
The Center for Cancer and Hematologic Disease
Cherry Hill, New Jersey, United States, 08003
United States, New Mexico
San Juan Oncology Associates
Farmington, New Mexico, United States, 87401
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
The Mark H. Zangmeister Center
Columbus, Ohio, United States, 43219
Signal Point Clinical Research
Middletown, Ohio, United States, 45042
United States, Virginia
Blueridge Cancer Care
Salem, Virginia, United States, 24153
United States, Washington
Northwest Medical Specialties
Tacoma, Washington, United States, 98405
United States, West Virginia
Mary Babb Randolph Cancer Center-Clinical Trials Unit
Morgantown, West Virginia, United States, 26506

Sponsors and Collaborators

OXiGENE

Investigators

Study Director:

Jai Balkissoon, MD

OXiGENE

More Information

Publications:

Lin CM, Singh SB, Chu PS, Dempcy RO, Schmidt JM, Pettit GR, Hamel E. Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study. Mol Pharmacol. 1988 Aug;34(2):200-8.

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.

Monestiroli S, Mancuso P, Burlini A, Pruneri G, Dell'Agnola C, Gobbi A, Martinelli G, Bertolini F. Kinetics and viability of circulating endothelial cells as surrogate angiogenesis marker in an animal model of human lymphoma. Cancer Res. 2001 Jun 1;61(11):4341-4.

Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997 Feb;18(1):4-25. Review. No abstract available.

Chaplin DJ, Pettit GR, Hill SA. Anti-vascular approaches to solid tumour therapy: evaluation of combretastatin A4 phosphate. Anticancer Res. 1999 Jan-Feb;19(1A):189-95.

Siemann DW, Mercer E, Lepler S, Rojiani AM. Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy. Int J Cancer. 2002 May 1;99(1):1-6.

Shaked Y, Ciarrocchi A, Franco M, Lee CR, Man S, Cheung AM, Hicklin DJ, Chaplin D, Foster FS, Benezra R, Kerbel RS. Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors. Science. 2006 Sep 22;313(5794):1785-7.

Responsible Party:	OXiGENE
ClinicalTrials.gov Identifier:	NCT00653939 History of Changes
Other Study ID Numbers:	OXC401-216
Study First Received:	March 18, 2008
Last Updated:	October 9, 2012
Health Authority:	United States: Food and Drug Administration India: Drugs Controller General of India

Keywords provided by OXiGENE:

non-small cell lung cancer
non-small cell lung carcinoma
neoplasms, lung
lung cancer
tumors

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
Combretastatin
Paclitaxel
Combretastatin A-4
Bevacizumab

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

ClinicalTrials.gov processed this record on May 21, 2013

A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-small Cell Lung Cancer (FALCON)