Pilot Study of Gut Microbiome Modulation to Enable Efficacy of Neoadjuvant Checkpoint-based Immunotherapy Following Chemotherapy in Pancreatic Adenocarcinoma
Icahn School of Medicine at Mount Sinai
Summary
A multi-institutional, single arm pilot study of antibiotics and pembrolizumab, following chemotherapy for the treatment of surgically resectable pancreatic cancer.
Description
Phase: Pilot Study Objectives Primary Objectives: • To determine the change in immune activation in pancreatic tumor tissue following treatment with antibiotics, pembrolizumab. Secondary Objectives: * To establish the safety and feasibility of pre-operative antibiotics in combination with pembrolizumab following chemotherapy * To describe the preliminary anti-tumor activity of pre-operative therapy with antibiotics, pembrolizumab, and chemotherapy in subjects with resectable pancreatic cancer Exploratory Objectives: * To determine immunophenotypic changes in the pancreatic tumor microenv…
Eligibility
- Age range
- 19+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Histologically confirmed pancreatic adenocarcinoma. Histologies other than adenocarcinoma, or any mixed histologies, will NOT be eligible. \*Note: histology must be confirmed prior to study treatment, however, participants may be consented to study based on imaging results consistent with pancreatic adenocarcinoma and then undergo diagnostic and research biopsy simultaneously. * Clinical stage T1-3, N0-2, M0 (per AJCC 8th ed) * Resectable pancreatic cancer as defined by NCCN Guidelines 2.2021 and based on pancreatic protocol dual-phase CT imaging. Multi-detector computed…
Interventions
- ProcedureBiopsy
Pre-treatment tumor biopsy
- DrugFOLFIRINOX
Patients will receive FOLFIRINOX chemotherapy every 2 weeks for 5 cycles. One cycle of mFOLFIRINOX = 14 days. Cycles of mFOLFIRINOX are delivered as follows\*: * Oxaliplatin: 85 mg/m2 IV over 2 hours on Day 1, followed by, * Irinotecan: 150 mg/m2 IV over 90 minutes on Day 1, followed by, * Leucovorin\*\*: 400 mg/m2 IV over 2 hours on Day 1, followed by, * 5FU: 2400 mg/m2 IV over 46-48 hours on Days 1-3
- DrugCiprofloxacin
Ciprofloxacin and metronidazole will be initiated 7 days following 5th dose of FOLFIRINOX. Subjects will self-administer ciprofloxacin 500mg PO BID on days 1-21. Participants will be instructed to take the antibiotics with food to minimize stomach upset and to administer at the same time each day. Treatment with antibiotics will continue for 21 days unless there is unacceptable toxicity or disease progression. Subjects will record date, time and number of tablets they take on provided drug diaries.
- DrugMetronidazole
Ciprofloxacin and metronidazole will be initiated 7 days following 5th dose of FOLFIRINOX. Subjects will self-administer metronidazole 500mg PO every 8 hours on days 1-21. Participants will be instructed to take the antibiotics with food to minimize stomach upset and to administer at the same time each day. Treatment with antibiotics will continue for 21 days unless there is unacceptable toxicity or disease progression. Subjects will record date, time and number of tablets they take on provided drug diaries.
Location
- Icahn School of Medicine at Mount SinaiNew York, New York