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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cholangiocarcinoma

Intervention / Treatment
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* Drug: RRx-001
* Drug: Gemcitabine and cisplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RRx-001 the cisplatin and gemcitabine<br>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<br>* 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<br>Drug: Gemcitabine and cisplatin<br>* 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<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| Disease control rate (DCR) |  | Up to 2 years | 
| Overall Survival |  | 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 |