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

Phase 2

Terminated

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
RRx-001 the cisplatin and gemcitabine	Gemcitabine and cisplatin	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
RRx-001 the cisplatin and gemcitabine	RRx-001	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

Primary Outcome Measures

Name	Time	Method
Overall Objective Response (RECIST)	Baseline and every 6-8 weeks while on treatment until progression. Estimated 8 -24 weeks.	Overall objective response (RECIST)

Secondary Outcome Measures