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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
OXiGENE
ClinicalTrials.gov Identifier:
NCT00653939
First received: March 18, 2008
Last updated: January 22, 2015
Last verified: January 2015
  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: Fosbretabulin
Drug: Carboplatin
Drug: Paclitaxel
Drug: Bevacizumab
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: 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)

Resource links provided by NLM:


Further study details as provided by OXiGENE:

Primary Outcome Measures:
  • Progression Free Survival (PFS) in the Intent-to-Treat Population [ Time Frame: Six 21-day cycles ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Best Overall Tumor Response Rate (RR) in the Intent-to-Treat Population [ Time Frame: Six 21-day cycles ] [ Designated as safety issue: No ]
    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.

  • Overall Survival (OS) Using a Multivariate Cox Regression Model in the Intent-to-Treat Population [ Time Frame: Until death or lost to follow-up, up to 12 months since randomization ] [ Designated as safety issue: No ]
  • Chemistry NCI-CTCAE Toxicity Grade of 3 or 4 (Safety Population) [ Time Frame: Days 1 (pretreatment) per 21-day Cycle (6 Cycles) ] [ Designated as safety issue: Yes ]
  • Hematology NCI-CTCAE Grade 3 or 4 (Safety Population) [ Time Frame: Days 1 (pretreatment), 7, 14, and 21 per 21-day Cycle (6 Cycles) ] [ Designated as safety issue: Yes ]
  • Coagulation NCI-CTCAE Grade 3 or 4 (Safety Population) [ Time Frame: Day 1 (pretreatment) per 21-day Cycle (6 Cycles) ] [ 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 on Day 1 of a 21-day cycle for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) alone on Day 1 every 3 weeks until progression or until 12 months from randomization.
Drug: Carboplatin
Chemotherapy: Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.
Other Name: Paraplatin
Drug: Paclitaxel
Chemotherapy: Paclitaxel (20 mg/m2) on Day 1 of each 21-day cycle for 6 cycles.
Other Name: Taxol
Drug: Bevacizumab
Bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle for 6 cycles.
Other Name: Avastin
Experimental: Arm 2: Active Comparator+Fosbretabulin
Carboplatin (AUC 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg), administered intravenously Day 1 of a 21-day cycle and fosbretabulin (60 mg/m2) on Days 7, 14, and 21 for up to six treatment cycles. After 6 cycles, subjects who have not progressed may continue to receive bevacizumab (15 mg/kg) on Day 1 and fosbretabulin on Days 1, 7 and 14 every 3 weeks until progression or until 12 months from randomization.
Drug: Fosbretabulin
Arm 2 only: Fosbretabulin (60 mg/m2) on Days 7,14 and 21 for 6 cycles.
Other Names:
  • Combretastatin A4 Phosphate
  • Zybrestat
  • CA4P
Drug: Carboplatin
Chemotherapy: Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.
Other Name: Paraplatin
Drug: Paclitaxel
Chemotherapy: Paclitaxel (20 mg/m2) on Day 1 of each 21-day cycle for 6 cycles.
Other Name: Taxol
Drug: Bevacizumab
Bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle for 6 cycles.
Other Name: Avastin

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 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.

  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 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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, Florida
Boca Raton Comprehensive Cancer Center
Boca Raton, Florida, United States, 21020
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, FACS OXiGENE
  More Information

Publications:
Responsible Party: OXiGENE
ClinicalTrials.gov Identifier: NCT00653939     History of Changes
Other Study ID Numbers: OXC401-216
Study First Received: March 18, 2008
Results First Received: January 14, 2015
Last Updated: January 22, 2015
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
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Bevacizumab
Carboplatin
Combretastatin
Fosbretabulin
Paclitaxel
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Growth Inhibitors
Growth Substances
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on July 01, 2015