Study Of Pembrolizumab With REOLYSIN® And Chemotherapy In Patients With Advanced Pancreatic Adenocarcinoma

Study Overview

Study of Pembrolizumab With REOLYSIN® and Chemotherapy in Patients With Advanced Pancreatic Adenocarcinoma

The purpose of this Phase 1b study is to investigate whether intravenous administration of REOLYSIN® in combination with chemotherapy and pembrolizumab is effective and safe in the treatment of pancreatic adenocarcinoma.

Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) is a naturally occurring, ubiquitous, non-enveloped human reovirus. It's primary mode of activity is to infect and selectively target tumors with activating Ras pathway mutations. Up to 70% of pancreatic cancers have activating Ras pathway mutations and/ or over-expressions. This is an open label, Phase 1b study of REOLYSIN® and chemotherapy in combination with pembrolizumab in patients with advanced (unresectable or metastatic) histologically confirmed pancreatic adenocarcinoma that progressed after (or did not tolerate) first-line therapy. It is thought that Reovirus when combined with chemotherapy would lead to increased viral replication and oncolysis preferentially in RAS activated tumors, with resulting immunogenic response than can be further enhanced by checkpoint inhibition using pembrolizumab. The study is designed to characterize the efficacy and safety of REOLYSIN® given intravenously in combination with one of the three chemotherapy backbone regimens, Gemcitabine, Irinotecan or Leucovorin/ 5-fluorouracil (5-FU), and pembrolizumab, the treatment cycle of which will be repeated every 3 weeks. It will follow a 3+3 design with no dose escalations. 3 patients will be initially enrolled. If no dose limiting toxicities (DLT) are observed, the cohort will be expanded. Provided patients do not develop intolerable toxicity (that does not respond to either supportive care or dose reduction) or clinically meaningful disease progression, treatment with additional cycles may be continued so long as patients experience clinical benefit in the judgement of the Investigator.

Pancreatic Adenocarcinoma

BIOLOGICAL: REOLYSIN®
DRUG: Chemotherapy
DRUG: Gemcitabine
DRUG: Irinotecan
DRUG: Leucovorin
DRUG: 5-fluorouracil
DRUG: Pembrolizumab

REO 024

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-11-25	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2018-09-12
First Submitted that Met QC Criteria 2015-12-02	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2018-09-13
First Posted (ACTUAL) 2015-12-03	Results First Posted N/A	Last Verified 2018-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Primary Outcome Measures	Measure Description	Time Frame
Determine the safety and DLTs of REOLYSIN® and chemotherapy (gemcitabine OR irinotecan OR 5FU) in combination with pembrolizumab in patients with advanced pancreatic adenocarcinoma who have progressed after (or did not tolerate) first line treatment		During the first cycle of treatment (3 week cycle)

Secondary Outcome Measures	Measure Description	Time Frame
Determine the overall response rate (ORR), and progression-free survival (PFS) by immune-related response criteria, as well as overall survival (OS)		Assessed every 9 weeks until disease progression or death. Post treatment scans every 3 months, if applicable.
Determine the effects of REOLYSIN® and pembrolizumab when administered in combination as determined by analysis of pre- and post-treatment biopsies and blood based immune markers		Biopsies (or available archival tumor tissue) performed before treatment begins and post treatment between Cycle 2 Day 15 and Cycle 3 Day 1. Immune marker analysis performed at start of treatment, Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 2 Day 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Have histologically confirmed advanced or metastatic pancreatic adenocarcinoma and have failed or did not tolerate first-line therapy.
Have either archival tissue available for immune testing OR if not, a baseline biopsy of a primary or metastatic lesion (including ascites) which is accessible for a biopsy that can be accomplished with reasonable safety.
Be available and agree to; a post-treatment tumor biopsy of either a primary or metastatic lesion (including ascites).
Have measurable disease.
Have no continuing acute toxic effects (except alopecia) of any prior anticancer treatment, i.e., all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE), version 4.02 [2], Grade ≤1. Any major surgery (except biopsies) must have occurred at least 28 days prior to study enrolment.
Have an ECOG Performance Score ≤ 2.
Have baseline laboratory results as follows:

Absolute neutrophil count (ANC) ≥ 1.5 x 10E9 [SI units 10E9/L].
Platelets ≥ 100 x10E9 [SI units 10E9/L] (without platelet transfusion)
Serum creatinine ≤ 1.5 x ULN.
Creatinine clearance (measured over 24 hours) OR calculated creatinine clearance (Cockcroft-Gault formula) of ≥ 60 mL/min.
Bilirubin ≤ 1.5 x ULN.
AST/ALT ≤ 3 x ULN (≤ 5 x ULN if patients have liver metastasis).
TSH, T4 and ACTH must be within normal range.
Proteinuria with normal or grade 1 OR Urinary protein < 1 g/24hr.
Negative pregnancy test for females of childbearing potential.
Have signed an informed consent indicating that the patient is aware of the neoplastic nature of their disease and have been informed of the procedures of the protocol, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
Be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests.

Receive concurrent therapy with any other investigational anticancer agent while on study.
Be on immunosuppressive therapy or have known HIV infection or active hepatitis B or C.
Receive radiotherapy within 28 days prior to receiving study drug.
Be a pregnant or breast-feeding woman. Female patients of childbearing potential must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. Barrier methods are a recommended form of contraception.
Have clinically significant cardiac disease (New York Heart Association, Class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, myocardial infarction 1 year prior to study entry, or grade 2 or higher compromised left ventricular ejection fraction.
Have dementia or altered mental status that would prohibit informed consent.
Have any other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Principal Investigator, would make the patient inappropriate for this study.
Have HIGH BURDEN/SYMPTOMATIC brain metastases. LOW VOLUME / ASYMPTOMATIC and pre-treated clinically stable brain metastases ARE allowed.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Sukeshi Patel Arora, MD, Cancer Therapy & Research Center at UTHSCSA

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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