Monoclonal Antibody RAV12 and Gemcitabine in Treating Patients With Metastatic Pancreatic Cancer
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. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving RAV12 together with gemcitabine may kill more tumor cells.
PURPOSE: This phase II trial is studying the side effects and best dose of monoclonal antibody RAV12 when given together with gemcitabine in treating patients with metastatic pancreatic cancer.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Evaluation of the Monoclonal Antibody, RAV12, in Combination With Standard Gemcitabine in the Treatment of Patients With Metastatic Pancreatic Cancer Who Have Not Been Previously Treated for Metastatic Disease|
- Proportion of Patients Alive at 8 Months [ Time Frame: 8 months ] [ Designated as safety issue: No ]
- Proportion of Patients Alive at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Partial Response and Complete Response Rates [ Time Frame: 8 months ] [ Designated as safety issue: No ]Based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.0; partial response = 30% decrease in sum of longest diameter. complete response = 100% decrease in sum of longest diameter. Rate of response = proportion of complete or partial responses based on number of patients evaluated.
- Progression-free Survival [ Time Frame: time to progression or death, up to 3 years ] [ Designated as safety issue: No ]
- Overall Survival [ Time Frame: three years ] [ Designated as safety issue: No ]
- Adverse Events [ Time Frame: any timeframe following study drug up to 3 years ] [ Designated as safety issue: Yes ]Frequency of adverse events and serious adverse events
- Cmax [ Time Frame: 29 days ] [ Designated as safety issue: No ]RAV12 and gemcitabine cmax
|Study Start Date:||March 2008|
|Study Completion Date:||March 2009|
|Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
|Experimental: RAV12 plus gemcitabine||
Biological: RAV12 plus gemcitabine
Initial dose of gemcitabine plus RAV12 at 0.375 mg/kg qw escalated to 0.75 mg/kg qw.
During the efficacy segment, 63 pts were to be treated with gemcitabine 1000 mg/m2 iv over 30 min., weekly days 1, 8, 15, 22 of the first cycle and 1000 mg/m2 iv over 30 min., weekly days 1, 8, and 15 of each subsequent cycle of 28 days plus RAV12 at Maximum Tolerated Dose (MTD) iv days 1; 4 or 5; 8, 11 or 12; and 15, 18 or 19 of each 28-day cycle until progression.
Other Name: gemcitabine: Gemzar
- To determine the maximum tolerated dose of monoclonal antibody RAV12 when administered with standard gemcitabine hydrochloride in patients with previously untreated metastatic pancreatic cancer.
- To determine the proportion of these patients surviving at 8 months after initiation of this regimen.
- To provide point estimates for response rate and duration of response in patients treated with this regimen.
- To define the toxicity profile of this drug in these patients when administered with standard gemcitabine hydrochloride.
- To estimate, preliminarily, the progression-free survival and overall survival of these patients after treatment with this regimen.
- To explore the utility of the tumor marker, carbohydrate antigen 19-9 (CA19-9), in the assessment of these patients.
OUTLINE: This is a dose-escalation study of monoclonal antibody RAV12, followed by an efficacy study. The study is conducted in two segments.
- Segment 1 (dose escalation of RAV12): Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, and 22 of course 1 and on days 1, 8, and 15 of each subsequent course. Patients also receive RAV12 IV once weekly on days 1, 8, and 15 or twice weekly on days 1, 4 or 5, 8, 11 or 12, 15, and 18 or 19 until the maximum tolerated dose (MTD) is reached. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
- Segment 2 (efficacy): Once the MTD has been determined, patients receive RAV12 at the MTD and gemcitabine hydrochloride as in segment 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are obtained for pharmacokinetic sampling during the dose-escalation segment of the study. Samples are analyzed to determine plasma concentrations of RAV12, gemcitabine hydrochloride, and difluorodeoxyuridine. Blood samples are also examined periodically for expression of serum biomarkers (i.e., CA19-9, RAAG12, and HACA) and for DNA analysis of Fc-gamma receptor polymorphisms. Archival paraffin blocks or slides from biopsy of primary or metastatic deposit or fresh/frozen tissue may be obtained at baseline for additional correlative studies. Samples are analyzed by immunohistochemistry (IHC) for expression of RAAG12 and for development of a companion RAAG12 diagnostic assay.
After completion of study therapy, patients are followed every 8 weeks for up to 3 years.
PROJECTED ACCRUAL: This study will accrue a total of 18 patients in the dose-escalation segment and 63 patients in the efficacy segment of the trial.
|United States, California|
|South San Francisco, California, United States, 94080|
|United States, Pennsylvania|
|Fox Chase Cancer Center - Philadelphia|
|Philadelphia, Pennsylvania, United States, 19111-2497|
|Study Chair:||Stanford Stewart, MD||MacroGenics, Incorporated|