External-Beam Radiation Therapy With or Without Indinavir and Ritonavir in Treating Patients With Brain Metastases

Oncology Institute of Southern Switzerland (IOSI)

Status and phase: Unknown; Phase 2

Conditions: Cancer

Treatments: Drug: ritonavir; Drug: indinavir sulfate; Radiation: radiation therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00637637

CDR0000587517 (Registry Identifier)

IOSI-RO0402

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Indinavir and ritonavir may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether external-beam radiation therapy is more effective with or without indinavir and ritonavir in treating patients with brain metastases.

PURPOSE: This randomized phase II trial is studying external-beam radiation therapy alone to see how well it works compared to external-beam radiation therapy given together with indinavir and ritonavir in treating patients with brain metastases.

Full description

OBJECTIVES:

• Compare the efficacy, in terms of time to treatment failure at CNS level and 4-months treatment failure rate, in patients with brain metastases treated with external-beam radiotherapy in combination with indinavir sulfate and ritonavir versus external-beam radiotherapy alone.
• Prospectively investigate the efficacy of a potentially antiangiogenic agent, indinavir sulfate.
• Investigate the antineoplastic activity of indinavir sulfate in combination with ionizing radiation in cancer patients with metastatic disease to the brain.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy to the brain once daily, 5 days a week for 2 weeks (10 doses total). Patients also receive oral indinavir sulfate and oral ritonavir twice daily for 35 days beginning at day 1 of radiotherapy.
• Arm II: Patients undergo radiotherapy to the brain once daily, 5 days a week for 2 weeks (10 doses total).

Patients complete quality of life questionnaires, including QOL-30 and the Mini Mental Status Examination, at baseline, 2 weeks after completion of radiotherapy, and at 1 and 3 months after completion of study treatment.

After completion of study treatment, patients are followed periodically for at least 4 months.

Enrollment: 60 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic cancer with brain metastases

  • Biopsy of brain metastases is not required

• All cancer types allowed, except for the following:

  • Prostatic adenocarcinoma
  • Sarcoma
  • Melanoma
  • Germ cell carcinoma,
  • Small-cell lung cancer

• Measurable disease by MRI of the brain

• Not requiring immediate surgical decompression (may qualify after surgery, if remaining measurable brain lesions)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2 (corresponds to recursive partitioning analysis groups I or II)
• Life expectancy > 4 months
• Able to understand the aim of trial and to comply with follow-up
• No HIV seropositivity

PRIOR CONCURRENT THERAPY:

• Prior dexamethasone allowed provided it is tapered before initiation of study radiotherapy
• Not requiring cytotoxic treatment within 3 months after study radiotherapy
• At least 1 week since prior and no concurrent phenytoin