Gut Microbiome Modulation to Enable Efficacy of Checkpoint-based Immunotherapy in Pancreatic Adenocarcinoma

NCT03891979 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: 18-00137
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

A multi-institutional, single arm pilot study of antibiotics and pembrolizumab for the treatment of surgically resectable pancreatic cancer. The primary purpose of this study is to determine the change in immune activation in pancreatic tumor tissue following treatment with antibiotics and pembrolizumab.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• Change in immune activation in pancreatic tumor tissue following treatment with antibiotics and pembrolizumab measured by activation of HLA-DR,

  activation is defined as an increase of 20% or more over baseline in percentage of T cells expressing the marker.

  12 Weeks

• Change in immune activation in pancreatic tumor tissue following treatment with antibiotics and pembrolizumab measured by activation of

  activation is defined as an increase of 20% or more over baseline in percentage of T cells expressing the marker.

  12 Weeks

Study Arms (1)

Pembrolizumab + Antibiotics

EXPERIMENTAL

Pembrolizumab will be given for two doses every 3 weeks starting on day 8 (ie days 8 and 29). Antibiotics will continue throughout the entire four week pre-operative period.

Drug: Pembrolizumab; Drug: Ciprofloxacin 500mg PO BID days 1-29; Drug: Metronidazole 500mg PO TID days 1-29

Interventions

Pembrolizumab DRUG

Pembrolizumab will be given for two doses every 3 weeks starting on day 8 (ie days 8 and 29). Antibiotics will continue throughout the entire four week pre-operative period. Ciprofloxacin 500mg PO BID days 1-29; Metronidazole 500mg PO TID days 1-29; Pembrolizumab 200mg IV days 8 and 29.

Pembrolizumab + Antibiotics

Ciprofloxacin 500mg PO BID days 1-29 DRUG

Antibiotics will continue throughout the entire four week pre-operative period.

Pembrolizumab + Antibiotics

Metronidazole 500mg PO TID days 1-29 DRUG

Antibiotics will continue throughout the entire four week pre-operative period.

Pembrolizumab + Antibiotics

Eligibility Criteria

• Age: 18 Months - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), 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 I and II disease (per AJCC 8th ed)
• Resectable pancreatic cancer as defined by NCCN Guidelines 1.2018 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
• Patients must agree to pre-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
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100 000/µL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
• Renal Creatinine OR Measured or calculated by creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR
• ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
• Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN

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 (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, 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 daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration except for adrenal replacement steroid doses \> 10 mg daily prednisone equivalent in the absence of active autoimmune disease.
• Note: Treatment with a short course of steroids (\< 5 days) up to 7 days prior to initiating study treatment is permitted. Participants with asthma that require intermittent use intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study.
• 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:
• Myocardial infarction or stroke/transient ischemic attack within the past 6 months
• Uncontrolled angina within the past 3 months
• Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
• History of other clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification III to IV, pericarditis, significant pericardial effusion, or myocarditis)
• Cardiovascular disease-related requirement for daily supplemental oxygen therapy.
• 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

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

pembrolizumab; Ciprofloxacin; Metronidazole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Deidre Cohen

  New York Langone Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: March 27, 2019
• Study Start: June 25, 2019
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: June 26, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: Upon reasonable request. Requests should be directed to Kirsten.Swingle@nyulangone.org. To gain access, data requestors will need to sign a data access agreement

Locations

US (1)