Whole Brain Radiation Therapy With Oxygen, With or Without RSR13, in Women With Brain Metastases From Breast Cancer

Study Overview
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Brief Summary
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RSR13 (efaproxiral) is a radiation sensitizer that has shown positive results in a Phase 3, randomized clinical trial of patients with brain metastases. Of 111 eligible breast cancer patients with brain metastases in that trial, 59 patients who received RSR13 prior to radiation therapy had a median survival time that was twice as long as the 52 patients who did not receive RSR13 prior to radiation therapy. RSR13 (efaproxiral) is an experimental drug that increases the amount of oxygen released from blood into the tissues. It is well known that certain types of cancer tumors, including those in brain metastases, lack oxygen. Lack of oxygen in a tumor can reduce the effect of radiation therapy (RT). RSR13 may increase the oxygen level in brain tumors so that radiation therapy works better. This study will enroll up to 360 women with brain metastases from breast cancer, and will evaluate if whole brain radiation therapy given with RSR13 will have a better treatment effect than whole brain radiation therapy alone. RSR13 will be infused intravenously (IV) through a central catheter placed in a central vein. Women randomized (assigned) to receive RSR13, therefore, will need to have a central catheter placed for treatment unless one is already in place.

Detailed Description
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The screening process will include documentation of the cancer, which which will require a brain scan and may include a liver scan. Other screening measurements will include a Karnofsky Performance Status (KPS) assessment, measurement of the amount of oxygen in the blood, using a non-invasive device most often placed on the finger, lung function tests that will require blowing into a machine, and an electrocardiogram (ECG). About 2 teaspoons, or 10 mL, of blood will be taken for specific laboratory tests, and a pregnancy test will be done on the blood of women of childbearing potential. All study patients will receive supplemental oxygen and whole brain radiation therapy (WBRT) (30 Gy, 3 Gy fractions) every weekday for 2 weeks. Half of the patients will be randomized (assigned) to receive RSR13 prior to WBRT, and will need to have a central catheter placed for treatment unless one is already in place. Patients who receive RSR13 will also need to continue to receive oxygen in the clinic until the amount of oxygen in their blood is near normal. This level has returned to near normal in most patients within 1 to 2 hours. During treatment and follow-up visits, physical and neurological exam, KPS assessment, weight, height, and vital sign measurements, and about 2 teaspoons of blood may be required. Patients will need to return for follow-up visits 1 month after completion of treatment, 2 months later, and every 3 months thereafter until their doctor tells them otherwise.

Official Title
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A Phase 3 Randomized, Open-label Comparative Study of Standard Whole Brain Radiation Therapy With Supplemental Oxygen, With or Without Concurrent RSR13 (Efaproxiral), in Women With Brain Metastases From Breast Cancer

Conditions
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Metastases, Breast Cancer

Intervention / Treatment
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* Drug: Efaproxiral
* Radiation: Whole Brain Radiation Therapy (WBRT)
* Other: Supplemental Oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult women with brain metastases from breast cancer Minimum KPS of 70 Exclusion Criteria: Previous treatment for brain metastases, including brain surgery and any form of radiation to the brain

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Efaproxiral + WBRT + Supplemental Oxygen<br> | Drug: Efaproxiral<br>* 75 mg/kg, administered over 30 minutes via a central venous access device (CVAD). Administered 30 minutes prior to the start of whole brain radiation therapy (WBRT) on each WBRT treatment day for 10 days.<br>* Other names: RSR13;Radiation: Whole Brain Radiation Therapy (WBRT)<br>* 3.0 Gy per day for 10 days (30.0 Gy total) of WBRT.<br>Other: Supplemental Oxygen<br>* 4 L/minute by nasal cannula. Administered at least 35 minutes prior to WBRT, during WBRT and until 15 minutes after completion of WBRT on all WBRT treatment days.<br>|
| Active Comparator: WBRT + Supplemental Oxygen<br> | Radiation: Whole Brain Radiation Therapy (WBRT)<br>* 3.0 Gy per day for 10 days (30.0 Gy total) of WBRT.<br>Other: Supplemental Oxygen<br>* 4 L/minute by nasal cannula. Administered at least 35 minutes prior to WBRT, during WBRT and until 15 minutes after completion of WBRT on all WBRT treatment days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | Measured from randomization until death due to any cause. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate in the Brain at 3 Months |  | Assessed at screening, 3 months after end of study treatment and at least 4 weeks after the 3-month scan. | 
| Karnofsky Performance Status & Neurological Signs & Symptoms |  | Assessed at baseline, 1 month follow-up (FU) visit, 3 month FU visit, and 6 month FU visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast, Brain, RSR13, efaproxiral, Whole Brain Radiation Therapy, Brain metastases, Metastatic breast cancer