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

February 6, 2024 updated by: ETOP IBCSG Partners Foundation

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

190

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Newly diagnosed, previously untreated (except for surgery, see below) asymptomatic or oligo-symptomatic brain metastases, e.g., controlled symptomatic seizure disorder. Note: patients with neurological symptoms or signs that require more than a stable dose of 4 mg dexamethasone equivalent for more than one week, are not considered oligo-symptomatic.

    Requirements for brain metastases:

    • Brain metastases must be previously untreated, except for surgery.
    • Prior surgery (including biopsies, resection, and cyst aspiration) for brain metastases is allowed. Residual and measurable disease after surgery is not required, but surgery must have confirmed the diagnosis. An MRI performed within 72 hours post-surgery should be available.
    • Number and size of metastases at diagnosis of brain metastases (as per Yamamoto et al.7):
    • Maximum 1-10 brain metastases
    • At least one brain metastasis must be of ≥5 mm in diameter
    • In case of 1-4 brain metastases:
    • Longest diameter of largest brain metastasis must be ≤30 mm
    • In case of 5-10 brain metastases:
    • Largest metastasis must be ≤10 mL in volume and longest diameter must be ≤30 mm
    • Maximum cumulative brain metastases volume must be ≤30 mL

  2. Primary disease of histologically confirmed (from primary tumour or from a metastatic lesion, including in the brain) melanoma or NSCLC

    Requirements for patients with melanoma:

    • Prior treatment, including treatment with immune-checkpoint inhibitors is permitted, but brain metastases must be newly diagnosed and previously untreated (except for surgery).
    • BRAF-mutation status, locally assessed, should be known (previous BRAF-targeted therapy is allowed).

    Requirements for patients with NSCLC:

    • Newly diagnosed, treatment-naïve (except for prior surgery) metastatic NSCLC, with or without a targetable oncogenic driver alteration: sensitising EGFR-mutation (exon 19-del and 21-L858R), ALK- or ROS1-fusion.
    • Known PD-L1 expression status (from primary tumour or from a metastatic lesion, including brain)
    • Known driver mutation status (from primary tumour or from a metastatic lesion, including brain).
  3. Age of 18 years or older
  4. Karnofsky performance status of 60 or more
  5. Life expectancy >12 weeks

  6. Patients must be candidates for systemic treatment, with one of the following treatment cohorts planned:

    • Immune-checkpoint inhibition therapy (combination of ipilimumab and nivolumab) for metastatic melanoma with or without a BRAF-mutation.
    • anti-PD-1/L1 monotherapy for metastatic melanoma with or without a BRAF-mutation.
    • targeted therapy for metastatic NSCLC with targetable oncogenic driver alteration (EGFR-mutation or ALK- or ROS1-fusion).
    • Immune-checkpoint inhibition therapy (including an anti-PD-1/L1 compound) alone or in combination with chemotherapy for metastatic NSCLC without targetable oncogenic driver alteration.
  7. Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 7 days before randomisation.
  8. Written IC for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention.

Exclusion Criteria:

  1. Confirmed or probable leptomeningeal metastasis according to EANO ESMO criteria1

  2. Symptomatic brain metastases at time of randomisation, e.g., neurological symptoms or signs that require more than a stable dose of 4 mg dexamethasone equivalent for more than one week.

    • Patients must be off steroids or on a stable dose of ≤4 mg dexamethasone equivalent for one week prior to randomisation.
    • Patients experiencing seizures controlled by anti-epileptic drugs are eligible.
  3. Prior whole brain irradiation or focal radiation therapy to the brain
  4. Prior systemic treatment for brain metastases
  5. Contra-indication for SRS
  6. For patients with NSCLC: any previous anticancer systemic therapy other than those under investigation in this study.
  7. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
  8. Women who are pregnant or in the period of lactation.
  9. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: standard systemic treatment with stereotactic radiosurgery (SRS)
Arm A
Radiation: Stereotactic radiosurgery

The following SRS therapy is foreseen: Two fractionation schedules according to radiation oncologist's preferences and patterns of brain metastases: 1 x 18-22 Gy (18-22 Gy) or 5 x 6 Gy (30 Gy).

The following fractionation schedules will be allowed (based on the latest AAPM report on a systematic review and dose response modelling):

  • Single fraction SRS (1 x 18-22 Gy) is the preferred schedule for 1-4 brain metastases, each with a longest diameter of ≤20 mm.
  • Fractionated SRT (5 x 6 Gy) is preferred for lesions >20 mm diameter or in case of the presence of 5-10 brain metastases.
  • For resection cavity irradiation the same selection criteria may be chosen.
Drug: Immune checkpoint inhibitor

Systemic therapy follows the current standard of care, according to the type of the primary tumour.

  • For patients in cohort 1a (Melanoma, treated with ipilimumab plus nivolumab), systemic therapy consists of the combination of ipilimumab plus nivolumab.
  • For patients in cohort 1b (Melanoma, treated with anti-PD-1/L1 monotherapy), systemic treatment consists of anti-PD-1/L1 monotherapy.
  • For patients in cohort 2a (NSCLC, treated with targeted therapy), systemic therapy consists of targeted therapy (EGFR-, ALK- or ROS1-targeted treatment).
  • For patients in cohort 2b (NSCLC, treated with anti-PD-1/L1 therapy with or without chemotherapy), systemic therapy consists of immune-checkpoint inhibition therapy (including an anti-PD-1/L1 compound) with or without chemotherapy.
Other Names:
  • standard of care treatment
Active Comparator: standard systemic treatment without stereotactic radiosurgery
Arm B
Drug: Immune checkpoint inhibitor

Systemic therapy follows the current standard of care, according to the type of the primary tumour.

  • For patients in cohort 1a (Melanoma, treated with ipilimumab plus nivolumab), systemic therapy consists of the combination of ipilimumab plus nivolumab.
  • For patients in cohort 1b (Melanoma, treated with anti-PD-1/L1 monotherapy), systemic treatment consists of anti-PD-1/L1 monotherapy.
  • For patients in cohort 2a (NSCLC, treated with targeted therapy), systemic therapy consists of targeted therapy (EGFR-, ALK- or ROS1-targeted treatment).
  • For patients in cohort 2b (NSCLC, treated with anti-PD-1/L1 therapy with or without chemotherapy), systemic therapy consists of immune-checkpoint inhibition therapy (including an anti-PD-1/L1 compound) with or without chemotherapy.
Other Names:
  • standard of care treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CNS-specific PFS, locally assessed as per iRANO criteria
Time Frame: from date of randomization until the date of documented CNS-specific progression, assessed up to 42 months
The primary objective of the study is to assess the efficacy in terms of CNS-specific progression-free survival (PFS) of the combination of standard systemic treatment plus SRS versus standard systemic treatment alone in patients with newly diagnosed and untreated (except surgery) asymptomatic or oligo-symptomatic brain metastases from melanoma or non-small cell lung cancer, with indication for systemic therapy.
from date of randomization until the date of documented CNS-specific progression, assessed up to 42 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ETOP IBCSG Partners Foundation

Collaborators

USZ Foundation

Investigators

  • Study Chair: Michael Weller, MD, University of Zurich
  • Study Chair: Rolf Stahel, MD, ETOP IBCSG Partners Foundation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 30, 2022

Primary Completion (Estimated)

January 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

August 23, 2022

First Submitted That Met QC Criteria

August 30, 2022

First Posted (Actual)

August 31, 2022

Study Record Updates

Last Update Posted (Actual)

February 7, 2024

Last Update Submitted That Met QC Criteria

February 6, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ETOP 19-21

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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