Dose-Escalation Study of RRx-001 in Combination With Whole Brain Radiation in Subjects With Brain Metastases

NCT ID: NCT02215512

Last Updated: 2021-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-06
• Study Completion Date: 2020-11-12

Brief Summary

In this dose-escalation study, the safety and tolerability of escalating dose levels of RRx-001 administered intravenously twice a week in subjects with brain metastases receiving whole brain radiation therapy (WBRT) will be assessed. Once a maximum tolerated dose is identified, further (up to approximately 30) participants will be recruited. The study will use MRI to monitor changes in tumor blood flow associated with RRx-001.

Detailed Description

The purpose of this research study is to test the safety and activity of whole brain radiation therapy with RRx-001, an experimental radiation sensitizer, in participants with brain metastases. As a radiation sensitizer, RRx-001 may increase the effect of whole brain radiation, the standard of care for brain metastases, on cancer cells in a specific target area while reducing damage to normal healthy cells. The ability to sensitize the cancer cells to radiation sets off a 'domino effect' of free radical damage in the tumor from a given amount or dose of radiation.

This study, which is called BRAINSTORM, since RRx-001 is associated with the development of a "free radical storm" in the brain tumors, is divided into two stages. In the first stage, approximately 3 participants at a time will be entered at a particular dose level of RRx-001 and then observed in order to see whether that dose results in side effects with radiation. If no bad side effects are observed, a second group of approximately 3 subjects will be given a slightly higher dose of RRx-001 and also monitored for side effects with radiation. This process will be repeated until a dose is reached, which has the most activity against the cancer cells without unacceptable side effects. At this point, more participants will be entered at this dose level until a maximum enrollment of approximately 30 participants has been reached.

RRx-001 releases a gas called nitric oxide, which widens the diameter of blood vessels, and allows the delivery of more oxygen to tumors. The presence of oxygen in tumors is critical for the effectiveness of radiation therapy, since cancer cells are about two to three times more vulnerable to radiation when oxygen is present. The reason that cancer cells are so much more vulnerable to the effects of radiation when oxygen is present is that radiation relies on the formation of harmful molecules known as free radicals that damage proteins and genetic material (DNA); without oxygen lower levels of free radicals are produced. Changes in the diameter go blood vessels will be studied by magnetic resonance imaging.

Unlike chemotherapies or other radiation sensitizers, RRx-001 does not have to enter the tumor to be effective because nitric oxide, as a gas, is able to spread or diffuse from the bloodstream into cancer cells.

Conditions

Brain Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RRx-001 + WBRT

RRx-001 administered intravenously twice a week (10, 17, 33, 55 mg) in subjects with brain metastases receiving whole brain radiation therapy (WBRT).

Group Type: EXPERIMENTAL

RRx-001 + WBRT

Intervention Type: DRUG

Subjects will receive a combination of RRx-001 and whole brain radiotherapy.

Interventions

RRx-001 + WBRT

Subjects will receive a combination of RRx-001 and whole brain radiotherapy.

Intervention Type: DRUG

Other Intervention Names

Whole brain radiotherapy and RRx-001

Eligibility Criteria

Inclusion Criteria

• Written informed consent
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• One or more brain metastases
• Prior radiation therapy to the brain is allowed with the exception of whole brain irradiation
• Subjects must be neurologically stable for at least 14 days prior to first dose of study drug;
• Male and female subjects who are not surgically sterile or post-menopausal must agree to use reliable methods of birth control for the duration of the study and for 90 days after the last dose of study drug administration; male partners of female subjects should use condoms for the duration of the study, and for 90 days after the last dose of study drug administration

Exclusion Criteria

• Pregnant or lactating females
• Any evidence of severe or uncontrolled diseases
• Inadequate bone marrow reserve
• Previous whole brain radiotherapy
• Prior RRx-001 therapy
• Insufficient recovery from all side effects of previous anticancer therapies
• Evidence of blood clotting or bleeding abnormalities

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EpicentRx, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michelle Kim, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

Providence Saint John's Health Center

Santa Monica, California, United States

University of Michigan

Ann Arbor, Michigan, United States

Allegiance Health

Jackson, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

The Cancer Institute of New Jersey (Rutgers University)

New Brunswick, New Jersey, United States

Countries

United States

Other Identifiers

RRx001-22-01

Identifier Type: -

Identifier Source: org_study_id