A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-Small Cell Lung Cancer

Tumors Clinical Trial

— FALCON  

Official title:

A Phase II Study to Assess the Safety and Efficacy of the Combination of Carboplatin, Paclitaxel, and Bevacizumab ± Combretastatin A4 Phosphate (CA4P) Followed by Bevacizumab ± CA4P in Subjects With Chemotherapy Naïve Stage IIIB/IV Non-Squamous Cell Histology Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00653939
• Other study ID #: OXC401-216
• Status: Completed
• Phase: Phase 2
• First received: March 18, 2008
• Last updated: January 22, 2015
• Start date: March 2008
• Est. completion date: October 2011

Study information

• Verified date: January 2015
• Source: OXiGENE
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIndia: Drugs Controller General of India
• Study type: Interventional

Clinical Trial Summary

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.

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 vascular endothelial growth factor (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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: October 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically confirmed Stage IIIB NSCLC with malignant pleural effusion, or Stage IV disease

• Measurable disease on CT scan (by the Response Evaluation Criteria in Solid Tumors [RECIST] criteria)

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Tumors

Intervention

Drug:
• Fosbretabulin
Arm 2 only: Fosbretabulin (60 mg/m2) on Days 7,14 and 21 for 6 cycles.
• Carboplatin
Chemotherapy: Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.
• Paclitaxel
Chemotherapy: Paclitaxel (20 mg/m2) on Day 1 of each 21-day cycle for 6 cycles.
• Bevacizumab
Bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle for 6 cycles.

Locations

Country	Name	City	State
United States	Boca Raton Comprehensive Cancer Center	Boca Raton	Florida
United States	Lahey Clinic Medical Center	Burlington	Massachusetts
United States	Southbay Oncology Hematology	Campbell	California
United States	Gabrail Cancer Center	Canton	Ohio
United States	The Center for Cancer and Hematologic Disease	Cherry Hill	New Jersey
United States	The Mark H. Zangmeister Center	Columbus	Ohio
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Pacific Coast Hematology and Oncology Medical Group	Fountain Valley	California
United States	UCLA Division of Hematology and Oncology	Los Angeles	California
United States	Kentuckiana Cancer Institute	Louisville	Kentucky
United States	Signal Point Clinical Research	Middletown	Ohio
United States	Mary Babb Randolph Cancer Center-Clinical Trials Unit	Morgantown	West Virginia
United States	Bay Area Cancer Research Group, LLC	Pleasant Hill	California
United States	Blueridge Cancer Care	Salem	Virginia
United States	Northwest Medical Specialties	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
OXiGENE

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997 Feb;18(1):4-25. Review. — View Citation

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. — View Citation

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. — View Citation

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. Erratum in: N Engl J Med. 2007 Jan 18;356(3):318. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) in the Intent-to-Treat Population	Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0. Based on 20% increase of the longest diameter of target lesions or appearance of one or more new non-target lesions or/and progression of non-target lesions since the treatment started.	Six 21-day cycles	No
Secondary	Best Overall Tumor Response Rate (RR) in the Intent-to-Treat Population	Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 for target lesions (assessed by MRI or CT scan): Complete Response (CR) is defined as the disappearance of all target lesions, Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, Progressive Disease is defined as at least 20% increase in the sum of the longest diameter of target lesions, Stable Disease (SD) is defined as neither shrinkage to qualify for a PR or increase to qualify for a PD.	Six 21-day cycles	No
Secondary	Overall Survival (OS) Using a Multivariate Cox Regression Model in the Intent-to-Treat Population		Until death or lost to follow-up, up to 12 months since randomization	No
Secondary	Chemistry NCI-CTCAE Toxicity Grade of 3 or 4 (Safety Population)		Days 1 (pretreatment) per 21-day Cycle (6 Cycles)	Yes
Secondary	Hematology NCI-CTCAE Grade 3 or 4 (Safety Population)		Days 1 (pretreatment), 7, 14, and 21 per 21-day Cycle (6 Cycles)	Yes
Secondary	Coagulation NCI-CTCAE Grade 3 or 4 (Safety Population)		Day 1 (pretreatment) per 21-day Cycle (6 Cycles)	Yes