Phase 1 Study of Adjuvant Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor-Transduced Pancreatic Tumor Cell Vaccine, Low-Dose Cyclophosphamide, and Stereotactic Body Radiation Therapy Followed by FOLFIRINOX in High-Risk Resected Pancreatic Ductal Adenocarcinoma.

Abstract

Purpose: Local and distant progression remains common following resection of resectable pancreatic ductal adenocarcinoma (PDAC) despite adjuvant multiagent chemotherapy. We report a prospective institutional phase 1 trial incorporating adjuvant GVAX vaccine, low-dose cyclophosphamide (Cy), and stereotactic body radiation therapy (SBRT) followed by FOLFIRINOX (FFX) among patients who underwent resection of high-risk PDAC.

Patients and methods: The study design was a modified 3+3. Cohort 1 received 5-fraction SBRT to 33 Gy to the tumor bed and 25 Gy to elective nodes followed by 6 cycles of full-dose FFX. After toxicity review, cohort 2 had SBRT and was switched to modified FFX (mFFX). Cohort 3 had 1 cycle of Cy/GVAX followed by SBRT, mFFX, and 4 cycles of maintenance Cy/GVAX with 6-month Cy/GVAX boosts until progression.

Results: Nineteen patients were enrolled with a median follow-up of 36.2 months. To be eligible, patients were required to have close/positive margins (within ≤1 mm) (71%) and/or lymph node metastasis (79%). Overall, 63% of patients had both. In cohort 1, 67% of patients received 6 cycles of FFX; in cohort 2, 75% received 6 cycles of modified FFX. In cohort 3, 12 patients received the first dose of Cy/GVAX and SBRT with 10 individuals (83%) receiving 6 cycles of mFFX. Cohort 3 had acceptable levels of grade ≥3 thrombocytopenia, neutropenia, and diarrhea after 2 cycles of mFFX. Median overall survival (OS)/disease-free survival (DFS) for the overall cohort and cohort 3 was 36.2/18.2 months and 61.3/24.1 months, respectively. One- and 2-year OS for cohort 3 was 83%/75%, respectively. At the last follow-up (median = x), 5 patients were alive (42%) in cohort 3.

Conclusions: This is the first prospective trial to evaluate adjuvant GVAX, Cy, SBRT, and mFFX in resected PDAC patients with high-risk features. This combination regimen was well tolerated with limited toxicity and promising survival outcomes, warranting future studies to validate this regimen in the adjuvant setting.