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
- 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
- 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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of Patients Alive at 8 Months
Stanford Stewart, MD
United States: Food and Drug Administration
|Fox Chase Cancer Center - Philadelphia||Philadelphia, Pennsylvania 19111-2497|
|MacroGenics, Incorporated||South San Francisco, California 94080|