Clinical trial NCT00653939: A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-Small Cell Lung Cancer
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tumors
Keywords: non-small cell lung cancer
non-small cell lung carcinoma
neoplasms, lung
lung cancer
tumors
NSCLC
Lead sponsor: Mateon Therapeutics
Sponsor class: INDUSTRY
First posted: 2008-04-07
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival (PFS) in the Intent-to-Treat Population
timeFrame: Six 21-day cycles
Secondary outcomes:
measure: Best Overall Tumor Response Rate (RR) in the Intent-to-Treat Population
timeFrame: Six 21-day cycles
measure: Overall Survival (OS) Using a Multivariate Cox Regression Model in the Intent-to-Treat Population
timeFrame: Until death or lost to follow-up, up to 12 months since randomization
measure: Chemistry NCI-CTCAE Toxicity Grade of 3 or 4 (Safety Population)
timeFrame: Days 1 (pretreatment) per 21-day Cycle (6 Cycles)
measure: Hematology NCI-CTCAE Grade 3 or 4 (Safety Population)
timeFrame: Days 1 (pretreatment), 7, 14, and 21 per 21-day Cycle (6 Cycles)
measure: Coagulation NCI-CTCAE Grade 3 or 4 (Safety Population)
timeFrame: Day 1 (pretreatment) per 21-day Cycle (6 Cycles)
Other outcomes:
Locations:
city: Campbell
country: United States
facility: Southbay Oncology Hematology
state: California
city: Fountain Valley
country: United States
facility: Pacific Coast Hematology and Oncology Medical Group
state: California
city: Los Angeles
country: United States
facility: UCLA Division of Hematology and Oncology
state: California
city: Pleasant Hill
country: United States
facility: Bay Area Cancer Research Group, LLC
state: California
city: Boca Raton
country: United States
facility: Boca Raton Comprehensive Cancer Center
state: Florida
city: Louisville
country: United States
facility: Kentuckiana Cancer Institute
state: Kentucky
city: Burlington
country: United States
facility: Lahey Clinic Medical Center
state: Massachusetts
city: Cherry Hill
country: United States
facility: The Center for Cancer and Hematologic Disease
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Columbus
country: United States
facility: The Mark H. Zangmeister Center
state: Ohio
city: Middletown
country: United States
facility: Signal Point Clinical Research
state: Ohio
city: Salem
country: United States
facility: Blueridge Cancer Care
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Morgantown
country: United States
facility: Mary Babb Randolph Cancer Center-Clinical Trials Unit
state: West Virginia
Study officials:
affiliation: Mateon Therapeutics
name: Jai Balkissoon, MD, FACS
role: STUDY_DIRECTOR
References:
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