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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02215512
First Posted: August 13, 2014
Last Update Posted: July 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
EpicentRx, Inc.
  Purpose
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.

Condition Intervention Phase
Brain Metastases Drug: RRx-001 + WBRT Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose-Escalation Study of RRx-001 in Combination With Whole Brain Radiation in Subjects With Brain Metastases (BRAINSTORM)

Further study details as provided by EpicentRx, Inc.:

Primary Outcome Measures:
  • Number, frequency and type of adverse events [ Time Frame: 42 days ]
    To identify the maximum tolerated dose (MTD) of RRx-001 in combination with WBRT, defined as the dose of RRx-001 associated with a 20% probability of dose-limiting toxicity (DLT) in subjects with brain metastases


Secondary Outcome Measures:
  • Objective Response Rate [ Time Frame: 4 months ]
    To assess the Objective Response Rate of RRx-001 in combination with WBRT using modified Response Evaluation Criteria in Solid Tumors

  • Clinical Benefit Rate [ Time Frame: 4 months ]
    To assess the Clinical Benefit Rate of RRx-001 in combination with WBRT using modified Response Evaluation Criteria in Solid Tumors

  • Intracranial Progression Free Survival [ Time Frame: 4 months ]
    To obtain a preliminary estimate of the efficacy of RRx-001 in combination with WBRT in prolonging intracranial Progression Free Survival in subjects with brain metastases

  • Overall Survival [ Time Frame: 10 months ]
    Overall Survival in subjects with brain metastases treated with WBRT and RRx-001

  • Brain Imaging Parameters [ Time Frame: 6 weeks ]
    To evaluate changes in imaging parameters of the brain as a surrogate measure of pharmacologic activity and neurocognitive outcome


Enrollment: 29
Actual Study Start Date: February 6, 2015
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
Drug: RRx-001 + WBRT
Subjects will receive a combination of RRx-001 and whole brain radiotherapy.
Other Name: Whole brain radiotherapy and 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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02215512


Locations
United States, California
Providence Saint John's Health Center
Santa Monica, California, United States, 90404
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Allegiance Health
Jackson, Michigan, United States, 49201
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New Jersey
The Cancer Institute of New Jersey (Rutgers University)
New Brunswick, New Jersey, United States, 08903
Sponsors and Collaborators
EpicentRx, Inc.
Investigators
Principal Investigator: Michelle Kim, MD University of Michigan
  More Information

Responsible Party: EpicentRx, Inc.
ClinicalTrials.gov Identifier: NCT02215512     History of Changes
Other Study ID Numbers: RRx001-22-01
First Submitted: August 11, 2014
First Posted: August 13, 2014
Last Update Posted: July 5, 2017
Last Verified: July 2017

Additional relevant MeSH terms:
Neoplasm Metastasis
Brain Neoplasms
Brain Diseases
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Central Nervous System Diseases
Nervous System Diseases