Dose-Escalation Study of RRx-001 in Combination With Whole Brain Radiation in Subjects With Brain Metastases (BRAINSTORM)
|ClinicalTrials.gov Identifier: NCT02215512|
Recruitment Status : Active, not recruiting
First Posted : August 13, 2014
Last Update Posted : July 5, 2017
|Condition or disease||Intervention/treatment||Phase|
|Brain Metastases||Drug: RRx-001 + WBRT||Phase 1|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Dose-Escalation Study of RRx-001 in Combination With Whole Brain Radiation in Subjects With Brain Metastases (BRAINSTORM)|
|Actual Study Start Date :||February 6, 2015|
|Estimated Primary Completion Date :||November 2017|
|Estimated Study Completion Date :||November 2017|
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
- 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
- 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02215512
|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|
|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|
|Principal Investigator:||Michelle Kim, MD||University of Michigan|