Testing the Addition of Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in People With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery

Metastatic Melanoma Clinical Trial

Official title: Phase III Trial of Salvage Stereotactic Radiosurgery (SRS) or SRS + Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for First or Second Distant Brain Relapse After Upfront SRS With Brain Metastasis Velocity >/= 4 Brain Metastases/Year

Status Recruiting

Clinical Trial Summary

This phase III trial compares the effect of adding whole brain radiotherapy with hippocampal avoidance and memantine to stereotactic radiosurgery versus stereotactic radiosurgery alone in treating patients with cancer that has spread to the brain and come back in other areas of the brain after earlier stereotactic radiosurgery. Hippocampus avoidance during whole-brain radiation therapy decreases the amount of radiation that is delivered to the hippocampus, which is a brain structure that is important for memory. The medicine memantine is also often given with whole brain radiation therapy because it may decrease the risk of side effects of radiation on thinking and memory. Stereotactic radiosurgery delivers a high dose of radiation only to the small areas of cancer in the brain and avoids the surrounding normal brain tissue. Adding whole brain radiotherapy with hippocampal avoidance and memantine to stereotactic radiosurgery may be effective in shrinking or stabilizing cancer that has spread to the brain and returned in other areas of the brain after receiving stereotactic radiosurgery.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine if salvage stereotactic radiosurgery (SRS) plus whole brain radiotherapy with hippocampal avoidance (HA-WBRT) in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS prolongs time to neurologic death as compared to salvage SRS alone.

SECONDARY OBJECTIVES:

I. To determine if salvage SRS + HA-WBRT in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS prolongs overall survival as compared to salvage SRS alone.

II. To evaluate if salvage SRS + HA-WBRT in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS prolongs intracranial progression-free survival as compared to salvage SRS alone.

III. To evaluate if salvage SRS + HA-WBRT in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS improves brain metastasis velocity at subsequent relapse as compared to salvage SRS alone.

IV. To assess perceived difficulties in cognitive abilities, symptom burden and health status after salvage SRS + HA-WBRT, as compared to salvage SRS alone, in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS.

V. To compare neurocognitive function outcomes following salvage SRS + HA-WBRT, as compared to salvage SRS alone, in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS.

VI. To tabulate and descriptively compare the adverse events associated with the interventions.

VII. To tabulate and descriptively compare the number of salvage procedures used to manage recurrent intracranial disease following the interventions.

EXPLORATORY OBJECTIVES:

I. To collect serum, plasma, and whole blood for translational research analyses.

II. To collect baseline and all follow-up magnetic resonance (MR) imaging for hippocampal volume, memory center substructures, axial T2 volumes, and quantitative texture analysis.

III. To collect baseline and follow-up MR imaging to extract whole brain volume, white matter volume and volume of metastatic disease to correlate with cognitive change at 4 months.

IV. To evaluate dose-volume histogram parameters to correlate with radiation toxicity.

V. To assess in patients receiving immunotherapy or targeted therapy, if salvage SRS + HA-WBRT in patients with brain metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS improves brain metastasis velocity and/or overall survival at subsequent relapse as compared to salvage SRS.

VI. To compare the estimated cost of brain-related therapies and quality-adjusted life years in patients who receive salvage SRS + HA-WBRT, as compared to salvage SRS alone, in patients with metastasis velocity >= 4 new brain metastases/year at time of first or second distant brain failure following upfront SRS.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo HA-WBRT daily (5 times weekly) for 2 weeks for a total of 10 fractions in the absence of disease progression or unacceptable toxicity. Within 1 week prior to or following HA-WBRT, patients undergo salvage SRS. Prior to HA-WBRT or no later than the 4th treatment, patients also receive memantine orally (PO) once daily (QD) or twice daily (BID) for 24 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo salvage SRS.

After completion of study treatment, patients are followed up every 2-3 months for at least 1 year. ;

Related Conditions & MeSH terms

• Anatomic Stage IV Breast Cancer AJCC v8
• Brain Neoplasms
• Breast Neoplasms
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Renal Cell
• Lung Neoplasms
• Metastatic Breast Carcinoma
• Metastatic Digestive System Carcinoma
• Metastatic Lung Non-Small Cell Carcinoma
• Metastatic Malignant Neoplasm in the Brain
• Metastatic Melanoma
• Metastatic Renal Cell Carcinoma
• Neoplasms
• Prognostic Stage IV Breast Cancer AJCC v8
• Recurrent Brain Neoplasm
• Stage IV Lung Cancer AJCC v8
• Stage IV Renal Cell Cancer AJCC v8
• Stage IVA Lung Cancer AJCC v8
• Stage IVB Lung Cancer AJCC v8

• NCT number: NCT04588246
• Study type: Interventional
• Source: NRG Oncology
• Status: Recruiting
• Phase: Phase 3
• Start date: December 15, 2020
• Completion date: January 31, 2030