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

Primary Purpose

Tumors

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fosbretabulin
Carboplatin
Paclitaxel
Bevacizumab
Sponsored by
Mateon Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tumors focused on measuring non-small cell lung cancer, non-small cell lung carcinoma, neoplasms, lung, lung cancer, tumors, NSCLC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Southbay Oncology Hematology
  • Pacific Coast Hematology and Oncology Medical Group
  • UCLA Division of Hematology and Oncology
  • Bay Area Cancer Research Group, LLC
  • Boca Raton Comprehensive Cancer Center
  • Kentuckiana Cancer Institute
  • Lahey Clinic Medical Center
  • The Center for Cancer and Hematologic Disease
  • San Juan Oncology Associates
  • Gabrail Cancer Center
  • The Mark H. Zangmeister Center
  • Signal Point Clinical Research
  • Blueridge Cancer Care
  • Northwest Medical Specialties
  • Mary Babb Randolph Cancer Center-Clinical Trials Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm 1: Chemotherapy+Bevacizumab

Arm 2: Active Comparator+Fosbretabulin

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Overall Survival (OS) Using a Multivariate Cox Regression Model in the Intent-to-Treat Population
Chemistry NCI-CTCAE Toxicity Grade of 3 or 4 (Safety Population)
Hematology NCI-CTCAE Grade 3 or 4 (Safety Population)
Coagulation NCI-CTCAE Grade 3 or 4 (Safety Population)

Full Information

First Posted
March 18, 2008
Last Updated
January 22, 2015
Sponsor
Mateon Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT00653939
Brief Title
A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-Small Cell Lung Cancer
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
October 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mateon Therapeutics

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tumors
Keywords
non-small cell lung cancer, non-small cell lung carcinoma, neoplasms, lung, lung cancer, tumors, NSCLC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Chemotherapy+Bevacizumab
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Arm 2: Active Comparator+Fosbretabulin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fosbretabulin
Other Intervention Name(s)
Combretastatin A4 Phosphate, Zybrestat, CA4P
Intervention Description
Arm 2 only: Fosbretabulin (60 mg/m2) on Days 7,14 and 21 for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Paraplatin
Intervention Description
Chemotherapy: Carboplatin (AUC 6) on Day 1 of each 21 day cycle for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxol
Intervention Description
Chemotherapy: Paclitaxel (20 mg/m2) on Day 1 of each 21-day cycle for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle for 6 cycles.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) in the Intent-to-Treat Population
Description
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.
Time Frame
Six 21-day cycles
Secondary Outcome Measure Information:
Title
Best Overall Tumor Response Rate (RR) in the Intent-to-Treat Population
Description
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.
Time Frame
Six 21-day cycles
Title
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
Title
Chemistry NCI-CTCAE Toxicity Grade of 3 or 4 (Safety Population)
Time Frame
Days 1 (pretreatment) per 21-day Cycle (6 Cycles)
Title
Hematology NCI-CTCAE Grade 3 or 4 (Safety Population)
Time Frame
Days 1 (pretreatment), 7, 14, and 21 per 21-day Cycle (6 Cycles)
Title
Coagulation NCI-CTCAE Grade 3 or 4 (Safety Population)
Time Frame
Day 1 (pretreatment) per 21-day Cycle (6 Cycles)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jai Balkissoon, MD, FACS
Organizational Affiliation
Mateon Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Southbay Oncology Hematology
City
Campbell
State/Province
California
ZIP/Postal Code
95008
Country
United States
Facility Name
Pacific Coast Hematology and Oncology Medical Group
City
Fountain Valley
State/Province
California
ZIP/Postal Code
92708
Country
United States
Facility Name
UCLA Division of Hematology and Oncology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Bay Area Cancer Research Group, LLC
City
Pleasant Hill
State/Province
California
ZIP/Postal Code
94523
Country
United States
Facility Name
Boca Raton Comprehensive Cancer Center
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
21020
Country
United States
Facility Name
Kentuckiana Cancer Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Lahey Clinic Medical Center
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
The Center for Cancer and Hematologic Disease
City
Cherry Hill
State/Province
New Jersey
ZIP/Postal Code
08003
Country
United States
Facility Name
San Juan Oncology Associates
City
Farmington
State/Province
New Mexico
ZIP/Postal Code
87401
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
The Mark H. Zangmeister Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43219
Country
United States
Facility Name
Signal Point Clinical Research
City
Middletown
State/Province
Ohio
ZIP/Postal Code
45042
Country
United States
Facility Name
Blueridge Cancer Care
City
Salem
State/Province
Virginia
ZIP/Postal Code
24153
Country
United States
Facility Name
Northwest Medical Specialties
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Mary Babb Randolph Cancer Center-Clinical Trials Unit
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
3412321
Citation
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Results Reference
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PubMed Identifier
17167137
Citation
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Results Reference
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PubMed Identifier
11389057
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.
Results Reference
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PubMed Identifier
9034784
Citation
Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997 Feb;18(1):4-25. doi: 10.1210/edrv.18.1.0287. No abstract available.
Results Reference
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PubMed Identifier
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Citation
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.
Results Reference
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PubMed Identifier
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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. doi: 10.1002/ijc.10316.
Results Reference
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PubMed Identifier
16990548
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. doi: 10.1126/science.1127592.
Results Reference
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A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-Small Cell Lung Cancer

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