RAV12 in Treating Patients With Metastatic or Recurrent Adenocarcinoma
RATIONALE: Monoclonal antibodies, such as RAV12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
PURPOSE: This phase I trial is studying the side effects and best dose of RAV12 in treating patients with metastatic or recurrent adenocarcinoma.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Multi-Dose Study of RAV12 (ANTI-RAAG12 MAB) in Patients With Metastatic or Recurrent Adenocarcinoma|
- Toxicity by CTCAE [ Time Frame: Days 1-50 ] [ Designated as safety issue: Yes ]
- Maximum tolerated dose [ Time Frame: Days 1-50 ] [ Designated as safety issue: Yes ]
- Pharmacokinetics of RAV12 by serum levels [ Time Frame: Days 1, 2, 4, 5, 8, 15, 22, 29, 36, 43, and 50 ] [ Designated as safety issue: No ]
- Immunogenicity by Human Anti-chimeric antibodies [ Time Frame: Days 1, 8, 15, 22, and 50 ] [ Designated as safety issue: Yes ]
- Time to tumor progression by clinical assessment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Progression free survival by clinical assessment [ Time Frame: 3 and 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||December 2004|
|Study Completion Date:||May 2008|
|Primary Completion Date:||May 2008 (Final data collection date for primary outcome measure)|
Biological: monoclonal antibody RAV12
Escalating doses of RAV12 (weekly 0.3, 1.0, 1.5, 3.0, 4.0, 5.0, 6.0 mg/kg or 0.5 mg/kg BIW or TIW; 0.75 mg/kg BIW) for 4 weeks
- Determine the maximum tolerated dose of RAV12 in patients with metastatic or recurrent adenocarcinoma.
- Determine the toxicity profile of this drug in these patients.
- Determine the pharmacokinetics and immunogenicity of this drug in these patients.
- Determine, preliminarily, the antitumor activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive RAV12 IV over 2 hours 2-3 times per week in weeks 1-4 (course 1). Patients are evaluated for response on day 43. Patients achieving a partial or complete response may be eligible to receive additional courses of RAV12 as above. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of RAV12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 15 additional patients are treated at the MTD in 1 or more patients groups (e.g., colorectal, pancreatic, gastroesophageal, and other adenocarcinoma).
After completion of study treatment, patients are followed within 4 weeks and then every 6-12 months thereafter.
PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.
|United States, California|
|Santa Monica, California, United States, 90404|
|United States, District of Columbia|
|Lombardi Comprehensive Cancer Center at Georgetown University Medical Center|
|Washington, District of Columbia, United States, 20007|
|United States, Florida|
|University of Miami Sylvester Comprehensive Cancer Center - Miami|
|Miami, Florida, United States, 33136|
|United States, Pennsylvania|
|Fox Chase Cancer Center - Philadelphia|
|Philadelphia, Pennsylvania, United States, 19111-2497|
|United States, Tennessee|
|Sarah Cannon Cancer Center at Centennial Medical Center|
|Nashville, Tennessee, United States, 37203|
|Study Director:||Stanford J Stewart, MD||MacroGenics|