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

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.
 
ClinicalTrials.gov Identifier: NCT02215512
Recruitment Status : Active, not recruiting
First Posted : August 13, 2014
Last Update Posted : November 20, 2019
Sponsor:
Information provided by (Responsible Party):
EpicentRx, Inc.

Tracking Information
First Submitted Date  ICMJE August 11, 2014
First Posted Date  ICMJE August 13, 2014
Last Update Posted Date November 20, 2019
Actual Study Start Date  ICMJE February 6, 2015
Actual Primary Completion Date November 28, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2014)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2014)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-Escalation Study of RRx-001 in Combination With Whole Brain Radiation in Subjects With Brain Metastases
Official Title  ICMJE A Phase 1 Dose-Escalation Study of RRx-001 in Combination With Whole Brain Radiation in Subjects With Brain Metastases (BRAINSTORM)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain Metastases
Intervention  ICMJE Drug: RRx-001 + WBRT
Subjects will receive a combination of RRx-001 and whole brain radiotherapy.
Other Name: Whole brain radiotherapy and RRx-001
Study Arms  ICMJE 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).
Intervention: Drug: RRx-001 + WBRT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 2, 2017)
29
Original Estimated Enrollment  ICMJE
 (submitted: August 11, 2014)
30
Estimated Study Completion Date  ICMJE June 2020
Actual Primary Completion Date November 28, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02215512
Other Study ID Numbers  ICMJE RRx001-22-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party EpicentRx, Inc.
Study Sponsor  ICMJE EpicentRx, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michelle Kim, MD University of Michigan
PRS Account EpicentRx, Inc.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP