Radiation Therapy With or Without RSR13 in Treating Patients With Brain Metastases

A Phase III, Randomized, Open-Label, Comparative Study of Standard Whole Brain Radiation Therapy With or Without RSR13 in Patients With Brain Metastases

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as RSR13 may make tumor cells more sensitive to radiation therapy.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy to the brain with or without RSR13 in treating patients who have brain metastases.

OBJECTIVES:

• Compare the median survival time in patients with brain metastases after receiving treatment with whole brain radiotherapy with or without RSR13.
• Compare the response rate to these treatment regimens in these patients.
• Compare the time to progression after receiving these treatment regimens in these patients.
• Compare quality of life in these patients receiving these treatment regimens.
• Compare cause of death (neurologic vs nonneurologic death) in these patients after receiving these treatment regimens.
• Determine the safety of RSR13 in these patients.
• Assess the pharmacokinetics of RSR13 in these patients.

OUTLINE: This is a randomized, open label, comparative, multicenter study. Patients are stratified according to the Radiation Therapy Oncology Group RPA Class (I vs II). Patients are further stratified within the RPA class II stratum according to site of primary cancer (non-small cell lung cancer vs breast vs other). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive whole brain radiotherapy 5 days a week for two weeks in conjunction with supplemental oxygen breathing.
• Arm II: Patients receive RSR13 IV over 30 minutes followed by whole brain radiotherapy and supplemental oxygen breathing as in arm I.

Quality of life is assessed at the first and last day of radiotherapy, at 1 month, 3 months, and then every 3 months until disease progression.

Patients are followed at 1 month, 3 months, every 3 months until disease progression, and then for survival.

PROJECTED ACCRUAL: A maximum of 408 (204 per treatment arm) patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Radiographically, histologically, or cytologically confirmed brain metastases with histologically or cytologically confirmed primary malignancy except the following:

  • Small cell lung cancer, germ cell tumors, and lymphomas

• No leptomeningeal metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Hemoglobin at least 10 g/dL
• WBC at least 2,000/mm3
• Platelet count at least 75,000/mm3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• ALT and AST no greater than 3 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Pulmonary:

• Forced vital capacity and forced expiratory volume at least 50% of normal in patients with significant intrathoracic tumor involvement, chronic obstructive pulmonary disease, interstitial lung disease, or pulmonary embolism
• Resting and exercise oxygen saturation at least 90% on room air

Other:

• No other concurrent active malignancy from a second histologic site
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy or immunotherapy for brain metastases
• At least 28 days since prior investigational biologic therapy

Chemotherapy:

• No prior chemotherapy for brain metastases
• No chemotherapy for brain metastases for at least one month following radiation therapy
• At least 7 days since prior chemotherapy for primary tumor or extracranial metastases
• No planned chemotherapy during radiation therapy

Endocrine therapy:

• No prior hormonal therapy for brain metastases
• Prior or concurrent corticosteroid therapy allowed

Radiotherapy:

• No prior whole brain radiotherapy for brain metastases
• No prior stereotactic radiosurgery for brain metastases

Surgery:

• Prior surgery allowed for brain metastases if at least one measurable lesion remains

Other:

• At least 28 days since prior investigational drug or device
• No prior RSR13