RRx-001 in Second Line Treatment of Advanced Cholangiocarcinoma Prior to Readministration of First-Line Therapy (EPIC)

A Phase 2, Single-Arm, Open-label, Study of RRx-001 in Second Line Treatment of Advanced Cholangiocarcinoma Prior to Readministration of First-Line Therapy

The purpose of this study is to see if the investigational drug, RRx-001, an epigenetic agent, which turns on a number of beneficial genes that the tumor has silenced, can resensitize the tumor(s), in other words make it/them re-respond to gemcitabine and cisplatin, which, hopefully, will translate to a longer lifespan. The name of the open-label study, which means that patients will know what treatments they are receiving, is EPIC, a hybrid or combination of EPIgenetic for the mechanism of action of RRx-001 and Cholangiocarcinoma.

The study treatment is divided into two stages. During the first stage, patients will receive RRx-001, which is administered intravenously weekly, for a fixed time period of six weeks. At that time the second stage starts in which cisplatin and gemcitabine are reintroduced for as long as the tumors respond to them to determine whether resensitization has occurred.

The primary objective of this clinical trial is to evaluate the progression-free survival (PFS) of patients at 9 weeks after the reintroduction of gemcitabine and cisplatin.

Study Overview

• Status: Terminated
• Conditions: Cholangiocarcinoma
• Intervention / Treatment: Drug: RRx-001; Drug: Gemcitabine and cisplatin

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of biliary tract adenocarcinoma/cholangiocarcinoma
• Must have locally advanced or distant metastatic disease that is not surgically curable
• Failed first-line chemotherapy
• Age ≥ 18 years
• Life expectancy of at least 12 weeks (3 months)
• Performance status 0 or 1
• Adequate liver, kidney, and bone marrow function

Exclusion Criteria:

• Symptomatic metastatic brain or meningeal tumors
• Investigational compound within 4 weeks of enrollment
• History of needing to permanently discontinue prior gemcitabine/ cisplatin regimen for reasons other than progression (i.e. toxicity)
• Any medical condition which, in the investigator's opinion, makes the patient unsuitable for participation
• Pregnant or nursing
• Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results
• Albumin <2.8
• Uncontrolled or clinically relevant ascites
• Absolute contraindication for MRI imaging such as intracorporeal metal or pacemaker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: RRx-001 the cisplatin and gemcitabine; Patients with advanced and metastatic biliary tract adenocarcinoma (cholangiocarcinoma) who had been treated with and failed first-line chemotherapy will be treated with RRx-001 (20 mg) intravenously weekly for up to six weeks followed by retreatment with Gemcitabine 1000 mg/m2 and Cisplatin 25 mg/m2 on Days 1 and 8 of a 21 Day Cycle until tumor progression

Drug: RRx-001; RRx-001 (10 mg/m2) intravenously twice weekly for up to six weeks followed by retreatment with Gemcitabine 1000 mg/m2 and Cisplatin 30 mg/m2 on Days 1 and 8 of a 21 Day Cycle until tumor progression; Drug: Gemcitabine and cisplatin; RRx-001 (20 mg) intravenously weekly for up to six weeks followed by retreatment with Gemcitabine 1000 mg/m2 and Cisplatin 25 mg/m2 on Days 1 and 8 of a 21 Day Cycle until tumor progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) of patients with advanced or metastatic biliary cancer after retreatment with gemcitabine and cisplatin following treatment with RRx-001	Progression-free survival (PFS) of patients with advanced or metastatic biliary cancer after retreatment with gemcitabine and cisplatin following treatment with RRx-001	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		Up to 2 years
Disease control rate (DCR)		Up to 2 years
Number, frequency and type of adverse events	Toxicity of gemcitabine and cisplatin following treatment with RRx-001	Up to 2 years

Collaborators and Investigators

• Sponsor: EpicentRx, Inc.
• Investigators: Principal Investigator: Ana De Jesus Acosta, MD, Johns Hopkins School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2015
• Primary Completion (Actual): May 10, 2016
• Study Completion (Actual): May 25, 2016

Study Registration Dates

• First Submitted: May 17, 2015
• First Submitted That Met QC Criteria: May 20, 2015
• First Posted (Estimate): May 25, 2015

Study Record Updates

• Last Update Posted (Actual): November 15, 2019
• Last Update Submitted That Met QC Criteria: November 13, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Cisplatin
• Other Study ID Numbers: RRx001-27-01