NCT05522660

Immunotherapy or Targeted Therapy With or Without Stereotactic Radiosurgery for Patients With Brain Metastases From Melanoma or Non-small Cell Lung Cancer

A Multicentre Randomised Open-label Phase III Study of Stereotactic Radiosurgery, in Addition to Standard Systemic Therapy for Patients With Metastatic Melanoma or Newly Diagnosed Metastatic NSCLC and Asymptomatic or Oligo-symptomatic Brain Metastases

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 180 (estimated)
• Sponsor: ETOP IBCSG Partners Foundation · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of the study is to assess the efficacy in terms of CNS-specific PFS of the combination of standard systemic treatment plus SRS vs. standard systemic treatment alone in patients with newly diagnosed and untreated (except for surgery) asymptomatic or oligosymptomatic brain metastases from melanoma or NSCLC. This proposed randomised phase III clinical study addresses one of the most controversial issues in the current approach to patients with brain mets: the timing of SRS in patients eligible for systemic immune checkpoint inhibition or targeted therapy in order to guide therapeutic options as to what strategy allows the best compromise between best survival and best QoL.

Conditions

• Non-Small Cell Lung Cancer
• Melanoma

Interventions

Type	Name	Description
RADIATION	Stereotactic radiosurgery	Depending on the investigator's preference, the following standard of care fractionation schedules are recommended: 1x 18-22 Gy, 3x 9 Gy or 5x 6 Gy. Fractionated stereotactic radiotherapy is favoured in principle, but not mandated, for postoperative radiotherapy and for metastases with a diameter of \>20 mm or for \>4 brain metastases. For patients randomised to Arm A, radiotherapy should be initiated within 14 days after randomisation.
DRUG	Immune checkpoint inhibitor	Systemic therapy follows the current standard of care, according to the type of the primary tumour. * For patients with melanoma, with or without BRAF-mutation, systemic therapy consists of * an approved immune-checkpoint inhibition combination therapy (cohort 1a) or * an approved immune-checkpoint inhibition monotherapy (cohort 1b). * For patients with NSCLC and a targetable oncogenic driver alteration (cohort 2a), systemic therapy consists of an approved targeted therapy (for example: EGFR-, ALK- or ROS1-targeted treatment). * For patients with NSCLC without a targetable oncogenic driver alteration (cohort 2b), systemic therapy consists of an approved immune-checkpoint inhibition therapy (with or without chemotherapy).

Timeline

• Start date: 2022-11-30
• Primary completion: 2026-01-01
• Completion: 2026-12-01
• First posted: 2022-08-31
• Last updated: 2025-12-11

Locations

15 sites across 5 countries: Italy, Netherlands, Spain, Switzerland, United Kingdom