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

NCT02620423 | Completed Phase 1 DMC

• 1 other identifier: REO 024
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatic Adenocarcinoma

Keywords

Pancreatic; Cancer; REOLYSIN®; Chemotherapy; Pembrolizumab; KEYTRUDA®; Pelareorep; Reovirus; Oncolytic virus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Interventions

REOLYSIN® BIOLOGICAL

4.5x10E10 TCID50 1 hour intravenous infusion, administered on Day 1 and 2 of a 21-day cycle

Also known as: Pelareorep

Chemotherapy DRUG

Patients may be treated with one of three chemotherapy backbone regimens. The decision on the chemotherapy backbone is based on physician preference.This includes either: a) Gemcitabine or b) Irinotecan or c)Leucovorin followed by 5-fluorouracil

Gemcitabine DRUG

1000 mg/m2 intravenous infusion over 30 minutes on Day 1 of a 21-day cycle or

Irinotecan DRUG

125 mg/m2 intravenous infusion over 90 minutes on Day 1 of a 21-day cyle or

Leucovorin DRUG

Leucovorin (LV) followed by 5-fluorouracil (5FU). LV 200 mg/m2 intravenous infusion over 2 hours on Day 1, 5FU 200 mg/m2 intravenous infusion bolus over 5-10 minutes on Day 1, followed by 5FU 1200 mg/m2 continuous intravenous infusion over 22 hours on Day 1 of a 21-day cycle

5-fluorouracil DRUG

Leucovorin (LV) followed by 5-fluorouracil (5FU). LV 200 mg/m2 intravenous infusion over 2 hours on Day 1, 5FU 200 mg/m2 intravenous infusion bolus over 5-10 minutes on Day 1, followed by 5FU 1200 mg/m2 continuous intravenous infusion over 22 hours on Day 1 of a 21-day cycle

Pembrolizumab DRUG

Pembrolizumab, 2 mg/kg intravenous infusion 30 minutes on Day 8 of a 21-day cycle

Also known as: KEYTRUDA®

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oncolytics Biotech: lead

Study Sites (1)

Cancer Therapy & Research Center at UTHSCSA

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

reolysin; Drug Therapy; Gemcitabine; Irinotecan; Leucovorin; Fluorouracil; pembrolizumab

Intervention Hierarchy (Ancestors)

Therapeutics; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones

Study Officials

• Sukeshi Patel Arora, MD

  Cancer Therapy & Research Center at UTHSCSA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2015
• First Posted: December 3, 2015
• Study Start: December 1, 2015
• Primary Completion: March 1, 2018
• Study Completion: August 1, 2018
• Last Updated: September 13, 2018

Record last verified: 2018-09

Locations

US (1)