Study Combining Suicide Gene Therapy With Chemoradiotherapy in the Treatment of Non-Metastatic Pancreatic Adenocarcinoma
The primary purpose of this phase I study is to determine the safety of combining replication-competent adenovirus-mediated suicide gene therapy with chemoradiotherapy in patients with non-metastatic pancreatic cancer.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study Combining Replication-Competent Adenovirus-Mediated Suicide Gene Therapy With Chemoradiotherapy for the Treatment of Non-Metastatic Pancreatic Adenocarcinoma|
- Toxicity [ Time Frame: 12 weeks post adenovirus injection ] [ Designated as safety issue: Yes ]
- Tumor response [ Time Frame: 3 - 12 months ] [ Designated as safety issue: No ]
- Time to progression [ Time Frame: 3 - 12 months ] [ Designated as safety issue: No ]
- Survival [ Time Frame: 10 - 20 months ] [ Designated as safety issue: No ]
- Gene expression in pancreas [ Time Frame: 1 - 14 days ] [ Designated as safety issue: No ]
|Study Start Date:||November 2006|
Experimental: Gene therapy
Adenovirus injection followed by 3 weeks of 5-FC + vGCV prodrug therapy and a 6 week course of capecitabine-based chemoradiation
Single injection on day 1 at one of five dose levels
The objectives of this study are:
To determine the toxicity and maximum tolerated dose (MTD) of the Ad5-yCD/mutTKSR39rep-ADP adenovirus in combination with 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy and standard chemoradiation. Fifteen to 30 subjects (5 cohorts of 3 - 6 subjects each) with non-metastatic, unresectable pancreatic cancer will receive a single intratumoral injection of the Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of five dose levels (1 x 10e10 vp, 3 x 10e10 vp, 1 x 10e11 vp, 3 x 10e11 vp, 1 x 10e12 vp) under endoscopic ultrasound (EUS)-guidance. Beginning three days later, subjects will receive 3 weeks (15 days) of 5-FC and vGCV prodrug therapy concomitant with a 6 week (30 day) course of capecitabine chemotherapy and 54 Gy conformal radiotherapy.
The primary endpoint is toxicity at 12 weeks. Secondary endpoints are: 1) tumor (radiological) response, 2) time to disease progression, 3) survival, 4) persistence of Ad5-yCD/mutTKSR39rep-ADP adenoviral DNA in blood, 5) infectious Ad5-yCD/mutTKSR39rep-ADP adenovirus in blood, and 6) HSV-1 TK gene expression in the pancreas.
|United States, Michigan|
|Henry Ford Health System|
|Detroit, Michigan, United States, 48202|
|Principal Investigator:||Munther Ajlouni, M.D.||Henry Ford Health System|