A Phase 2 Randomized, Open-Label Study of RRx-001 vs Regorafenib in Subjects With Metastatic Colorectal Cancer

NCT02096354 | Completed Phase 2 Results DMC

• 1 other identifier: RRx001-21-02
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 5

Brief Summary

This two-stage study is designed to compare the safety and activity between RRx-001 against regorafenib followed by irinotecan-based therapies in a parallel comparative study. Patients who are suffering from advanced or metastatic (meaning the disease has spread) colorectal cancer are invited to participate in this study. There will be two groups of patients (Randomized, open label study), one of these will receive RRx-001 and the other one will receive regorafenib. If patients qualify to participate in this study, they will be randomly assigned to the 'interventional arm' where patients will receive the experimental drug, RRx-001, or the 'control arm' where they will receive the current standard-of-care, Regorafenib. Patients have a 66% chance (2 out of 3) of receiving RRx-001 and a 33 % chance (1 out of 3) of receiving regorafenib. On progression in the first part of the study, provided ECOG performance status is adequate, and if clinically appropriate i.e. there are no absolute or relative contraindications in the opinion of the Investigator, all subjects will enter the second part of the study and receive irinotecan plus bevacizumab. Whether patients are given RRx-001 or regorafenib, they will also receive best supportive care, which includes treatments to help manage side effects and symptoms of cancer. This is an open label study, which means patients will know to which of these treatments, RRx-001 or regorafenib, they are assigned.

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 47 months

  From date of enrollment until death or censorship.

Secondary Outcomes (4)

• Progression Free Survival

  Baseline, every 6-8 weeks while on study.

• Number of Adverse Events

  Baseline through end of treatment (28 days after last dose of study drug). Approximately 24 weeks.

• Objective Response Rate

  Up to 2 years

• Clinical Benefit Rate

  Up to 2 years

Study Arms (2)

RRx-001 followed by irinotecan

EXPERIMENTAL

Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)

Drug: RRx-001; Drug: Irinotecan

Regorafenib followed by irinotecan

ACTIVE COMPARATOR

Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)

Drug: Regorafenib; Drug: Irinotecan

Interventions

RRx-001 DRUG

RRx-001 followed by irinotecan

Regorafenib DRUG

Also known as: Stivarga

Regorafenib followed by irinotecan

Irinotecan DRUG

To be dosed after RRx-001 or regorafenib

Also known as: With or without bevacizumab

RRx-001 followed by irinotecan; Regorafenib followed by irinotecan

Eligibility Criteria

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

You may qualify if:

• Histological or cytological documentation of adenocarcinoma of the colon or rectum;
• Subject must have received at least oxaliplatin-, and irinotecan-based regimens with bevacizumab and with, cetuximab or panitumumab if KRAS wildtype and are refractory to irinotecan;
• Subject has measurable disease by radiographic techniques (computerized tomography \[CT\] or magnetic resonance imaging \[MRI\]);
• Subjects with a history of brain metastasis are eligible for the study as long as they meet all the following criteria: their brain metastases have been treated, they have no evidence of progression or hemorrhage after treatment, have been off dexamethasone for 4 weeks prior to first study drug administration, and have no ongoing requirement for dexamethasone or anti-epileptic drugs;
• Life expectancy of at least 12 weeks
• Subject's Eastern Cooperative Group (ECOG) performance status is 0 or 1;
• Adequate organ function
• Fertile subjects must use effective contraception during the course of the study and for 30 days following withdrawal from the study;

You may not qualify if:

• Clinically significant cardiovascular disease;
• Unresolved toxicity higher attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin- induced neurotoxicity ≤ Grade 2 for at least 14 days;
• Evidence or history of tendency or predisposition to active bleeding. Any hemorrhage or bleeding event of Grade 3 or higher within 4 weeks of start of study medication;
• Symptoms or signs of active brain metastases;
• History of an allergic reaction or intolerance to irinotecan
• Hepatic encephalopathy
• Cholangitis that required treatment or intervention within 4 weeks of study enrollment
• Concurrent anticancer therapy or any cytotoxic therapy within 1 month prior to Day 1. Corticosteroid therapy is not allowed except on dosing days;
• Subject has previously received regorafenib;
• Clear contraindication for systemic corticosteroids (diabetes mellitus is not per se a clear contraindication);
• Severe hypoalbuminemia (albumin \< 3.0 g/dL);
• Subjects who are pregnant or lactating or who are planning to become pregnant during the course of the study are excluded.

Sponsors & Collaborators

• EpicentRx, Inc.: lead

Study Sites (5)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Kaiser Permanete

Honolulu, Hawaii, 96819, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Aquilino Cancer Center, Maryland Oncology and Hematology PA

Rockville, Maryland, 20850, United States

Location

Related Publications (4)

• Oronsky B, Scribner C, Aggarwal R, Cabrales P. RRx-001 protects normal tissues but not tumors via Nrf2 induction and Bcl-2 inhibition. J Cancer Res Clin Oncol. 2019 Aug;145(8):2045-2050. doi: 10.1007/s00432-019-02958-4. Epub 2019 Jun 27.

  PMID: 31250159 BACKGROUND

• Scicinski J, Fisher G, Carter C, Cho-Phan C, Kunz P, Ning S, Knox S, Oronsky B, Caroen S, Parker C, Fanger G, Reid T. The Development Of RRx-001, A Novel Nitric-Oxide-Mediated Epigenetically Active Anticancer Agent. Redox Biol. 2015 Aug;5:422. doi: 10.1016/j.redox.2015.09.035. Epub 2015 Dec 30.

  PMID: 28162292 BACKGROUND

• Reid TR, Abrouk N, Caroen S, Oronsky B, Stirn M, Larson C, Beale K, Knox SJ, Fisher G. ROCKET: Phase II Randomized, Active-controlled, Multicenter Trial to Assess the Safety and Efficacy of RRx-001 + Irinotecan vs. Single-agent Regorafenib in Third/Fourth Line Colorectal Cancer. Clin Colorectal Cancer. 2023 Mar;22(1):92-99. doi: 10.1016/j.clcc.2022.11.003. Epub 2022 Dec 2.

  PMID: 36529613 RESULT

• Reid T, Dad S, Korn R, Oronsky B, Knox S, Scicinski J. Two Case Reports of Resensitization to Previous Chemotherapy with the Novel Hypoxia-Activated Hypomethylating Anticancer Agent RRx-001 in Metastatic Colorectal Cancer Patients. Case Rep Oncol. 2014 Jan 24;7(1):79-85. doi: 10.1159/000358382. eCollection 2014 Jan.

  PMID: 24575021 RESULT

Related Links

• EpicentRx, Inc Home page.

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

RRx-001; regorafenib; Irinotecan; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director: Bryan Oronsky, Chief Medical Officer
• Organization: EpicentRx, Inc

boronsky@epicentrx.com

858-229-1062

Study Officials

• Bryan Oronsky, MD

  EpicentRx, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2014
• First Posted: March 26, 2014
• Study Start: May 1, 2014
• Primary Completion: April 13, 2018
• Study Completion: October 8, 2020
• Last Updated: October 15, 2024
• Results First Posted: October 15, 2024

Record last verified: 2024-09

Locations

US (5)