Modulation of the Gut Microbiome With Pembrolizumab Following Chemotherapy in Resectable Pancreatic Cancer

NCT05462496 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY-21-01814
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

A multi-institutional, single arm pilot study of antibiotics and pembrolizumab, following chemotherapy for the treatment of surgically resectable pancreatic cancer.

Conditions

Pancreatic Cancer

Keywords

Pancreatic cancer; antibiotics; resectable; microbiome; pembrolizumab; chemotherapy

Outcome Measures

Primary Outcomes (2)

• Achievement of overall immune response

  Achievement of overall immune response, defined as activation of one or more of the following T cell markers: HLA-DR, CD38, CD25, KI67, and CD69; activation is defined as an increase of 20% or more over baseline in percentage of T cells expressing the marker. Comparison to be made between tissue biopsy taken following chemotherapy (and prior to antibiotics and pembrolizumab) and definitive surgical specimen.

  at day 43

• Achievement of overall immune response

  Achievement of overall immune response, defined as activation of one or more of the following T cell markers: HLA-DR, CD38, CD25, KI67, and CD69; activation is defined as an increase of 20% or more over baseline in percentage of T cells expressing the marker. Comparison to be made between tissue biopsy taken following chemotherapy (and prior to antibiotics and pembrolizumab) and definitive surgical specimen.

  day 102

Secondary Outcomes (5)

• Adverse event incidence rate

  at 6 months

• R0 resection rate

  at 3-4 months

• Proportion of participants with histologic regression score 0, 1, or 2

  at 3-4 months

• Overall response rate (ORR)

  at 3-4 months

• Overall survival rate (OS)

  at 5 years

Study Arms (1)

Participants who had Chemotherapy Following Pancreatic Adenocarcinoma

EXPERIMENTAL

Participants to be given antibiotics and pembrolizumab, following chemotherapy for the treatment of surgically resectable pancreatic cancer.

Procedure: Biopsy; Drug: FOLFIRINOX; Drug: Ciprofloxacin; Drug: Metronidazole; Drug: Pembrolizumab; Procedure: Surgical Resection

Interventions

Biopsy PROCEDURE

Pre-treatment tumor biopsy

Participants who had Chemotherapy Following Pancreatic Adenocarcinoma

FOLFIRINOX DRUG

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

Also known as: Chemotherapy

Participants who had Chemotherapy Following Pancreatic Adenocarcinoma

Ciprofloxacin DRUG

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.

Also known as: Antibiotic

Participants who had Chemotherapy Following Pancreatic Adenocarcinoma

Metronidazole DRUG

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.

Also known as: Antibiotic

Participants who had Chemotherapy Following Pancreatic Adenocarcinoma

Pembrolizumab DRUG

Pembrolizumab will be initiated 7 days post initiation of antibiotics. Subjects will receive a flat dose of pembrolizumab 200mg IV over 30 minutes.

Also known as: Immunotherapy, Monoclonal antibody

Participants who had Chemotherapy Following Pancreatic Adenocarcinoma

Surgical Resection PROCEDURE

Following completion of 21 days of antibiotics, participant will undergo repeat imaging studies. If there is no progressive disease which renders participant surgically unresectable (based on NCCN guidelines 2.2021), subject will undergo definitive surgical resection.

Also known as: pancreaticoduodenectomy, pancreatectomy

Participants who had Chemotherapy Following Pancreatic Adenocarcinoma

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 tomography (MDCT) angiography, performed by acquiring thin, preferably sub-millimeter, axial sections using a dual-phase pancreatic protocol, with images obtained in the pancreatic and portal venous phase of contrast enhancement, is required.
• No arterial tumor contact (celiac axis \[CA\], superior mesenteric artery \[SMA\], or common hepatic artery \[CHA\])
• No tumor contact with the superior mesenteric vein (SMV) or portal vein (PV) or ≤180° contact without vein contour irregularity
• Age \> 18 years
• Patients must agree to pre-treatment biopsy(which may have been collected on a universal consent), on-treatment biopsy, and definitive surgical resection
• ECOG performance status of 0 or 1
• No prior treatment for diagnosis of pancreatic cancer
• Normal organ and marrow function as defined below:
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100 000/µL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. )
• Creatinine ≤1.5 × ULN OR Measured or calculated creatinine clearance (Creatinine clearance (CrCl) should be calculated per institutional standard., GFR can also be used in place of creatinine or CrCl) ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN; ; GFR=glomerular filtration rate; ULN=upper limit of normal .
• Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN AST (SGOT) and ALT (SGPT) ≤2.5 × ULN; ALT (SGPT) =alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT) =aspartate aminotransferase (serum glutamic oxaloacetic transaminase);

You may not qualify if:

• Borderline resectable, locally advanced or distant metastatic disease
• Any medical condition which makes definitive surgical resection of the pancreatic cancer contraindicated due to high risk of morbidity/mortality
• Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Medical history and concurrent disease as below:
• Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity.
• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
• Evidence of uncontrolled, active infection, requiring parenteral or oral anti-bacterial, anti-viral or anti-fungal therapy ≤ 28 days prior to screening on study.
• Participants with a condition requiring chronic systemic oral treatment with either antibiotics or anti-fungals
• Any uncontrolled inflammatory GI disease including Crohn's Disease and ulcerative colitis.
• Participants with active, known, or suspected autoimmune disease.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. \*Note: for those participants who will be undergoing planned splenectomy, vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus may be administered per standard practice.
• Use of probiotics ≤ 28 days prior to screening on study.
• Known human immunodeficiency virus (HIV), known active Hepatitis A, or known Hepatitis B
• History of acute diverticulitis within the last 6 months or current chronic diarrhea

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Biopsy; folfirinox; Drug Therapy; Ciprofloxacin; Anti-Bacterial Agents; Metronidazole; pembrolizumab; Immunotherapy; Antibodies, Monoclonal; Pancreaticoduodenectomy; Pancreatectomy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Therapeutics; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Immunomodulation; Biological Therapy; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Digestive System Surgical Procedures

Study Officials

• Deirdre Cohen, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deirdre Cohen, MD

CONTACT

(212) 824-9331; Deirdre.Cohen@mssm.edu

Rashmi Unawane

CONTACT

rashmi.unawane@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Gastrointestinal (GI) Oncology Program, Associate Professor of Medicine (Hematology and Medical Oncology),

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: July 18, 2022
• Study Start: March 16, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: As soon as possible after publication - to be determined
• Access Criteria: Researchers who provide a methodologically sound proposal. Any purpose. At Principal Investigator discretion (Deirdre.Cohen@mssm.edu)

Locations

US (1)