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

NCT00653939 | Completed Phase 2 Results DMC

• 1 other identifier: OXC401-216
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 15

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.

Conditions

Tumors

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Best Overall Tumor Response Rate (RR) in the Intent-to-Treat Population

  Six 21-day cycles

• 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

• Chemistry NCI-CTCAE Toxicity Grade of 3 or 4 (Safety Population)

  Days 1 (pretreatment) per 21-day Cycle (6 Cycles)

• Hematology NCI-CTCAE Grade 3 or 4 (Safety Population)

  Days 1 (pretreatment), 7, 14, and 21 per 21-day Cycle (6 Cycles)

• Coagulation NCI-CTCAE Grade 3 or 4 (Safety Population)

  Day 1 (pretreatment) per 21-day Cycle (6 Cycles)

Study Arms (2)

Arm 1: Chemotherapy+Bevacizumab

ACTIVE COMPARATOR

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; Drug: Paclitaxel; Drug: Bevacizumab

Arm 2: Active Comparator+Fosbretabulin

EXPERIMENTAL

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; Drug: Carboplatin; Drug: Paclitaxel; Drug: Bevacizumab

Interventions

Fosbretabulin DRUG

Arm 2 only: Fosbretabulin (60 mg/m2) on Days 7,14 and 21 for 6 cycles.

Also known as: Combretastatin A4 Phosphate, Zybrestat, CA4P

Arm 2: Active Comparator+Fosbretabulin

Carboplatin DRUG

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

Also known as: Paraplatin

Arm 1: Chemotherapy+Bevacizumab; Arm 2: Active Comparator+Fosbretabulin

Paclitaxel DRUG

Chemotherapy: Paclitaxel (20 mg/m2) on Day 1 of each 21-day cycle for 6 cycles.

Also known as: Taxol

Arm 1: Chemotherapy+Bevacizumab; Arm 2: Active Comparator+Fosbretabulin

Bevacizumab DRUG

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

Also known as: Avastin

Arm 1: Chemotherapy+Bevacizumab; Arm 2: Active Comparator+Fosbretabulin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mateon Therapeutics: lead

Study Sites (15)

Southbay Oncology Hematology

Campbell, California, 95008, United States

Location

Pacific Coast Hematology and Oncology Medical Group

Fountain Valley, California, 92708, United States

Location

UCLA Division of Hematology and Oncology

Los Angeles, California, 90095, United States

Location

Bay Area Cancer Research Group, LLC

Pleasant Hill, California, 94523, United States

Location

Boca Raton Comprehensive Cancer Center

Boca Raton, Florida, 21020, United States

Location

Kentuckiana Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Lahey Clinic Medical Center

Burlington, Massachusetts, 01805, United States

Location

The Center for Cancer and Hematologic Disease

Cherry Hill, New Jersey, 08003, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

The Mark H. Zangmeister Center

Columbus, Ohio, 43219, United States

Location

Signal Point Clinical Research

Middletown, Ohio, 45042, United States

Location

Blueridge Cancer Care

Salem, Virginia, 24153, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Mary Babb Randolph Cancer Center-Clinical Trials Unit

Morgantown, West Virginia, 26506, United States

Location

Related Publications (7)

• 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.

  PMID: 3412321 BACKGROUND

• 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. doi: 10.1056/NEJMoa061884.

  PMID: 17167137 BACKGROUND

• 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.

  PMID: 11389057 BACKGROUND

• 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.

  PMID: 9034784 BACKGROUND

• 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.

  PMID: 10226542 BACKGROUND

• 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.

  PMID: 11948484 BACKGROUND

• 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.

  PMID: 16990548 BACKGROUND

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

fosbretabulin; Carboplatin; Paclitaxel; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Chief Executive Officer
• Organization: OXiGENE, Inc.

info@oxigene.com

650-635-7000

Study Officials

• Jai Balkissoon, MD, FACS

  Mateon Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2008
• First Posted: April 7, 2008
• Study Start: March 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: October 1, 2011
• Last Updated: February 9, 2015
• Results First Posted: February 9, 2015

Record last verified: 2015-01

Locations

US (15)