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

Primary Purpose

Non-Small Cell Lung Cancer, Melanoma

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Stereotactic radiosurgery
Immune checkpoint inhibitor
Sponsored by
ETOP IBCSG Partners Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
  • Santa Maria della Misericordia Hospital
  • Istituto Nazionale Tumori "Regina Elena"
  • Policlinico Umberto 1
  • Azienda ospedaliero-universitaria Senese SienaRecruiting
  • NKI-AVLRecruiting
  • InselspitalRecruiting
  • Kantonsspital Winterthur
  • Universitätsspital ZürichRecruiting
  • Royal Marsden (Sutton)
  • Christie NHS Manchester

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

standard systemic treatment with stereotactic radiosurgery (SRS)

standard systemic treatment without stereotactic radiosurgery

Arm Description

Arm A

Arm B

Outcomes

Primary Outcome Measures

CNS-specific PFS, locally assessed as per iRANO criteria
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.

Secondary Outcome Measures

Full Information

First Posted
August 23, 2022
Last Updated
July 17, 2023
Sponsor
ETOP IBCSG Partners Foundation
Collaborators
USZ Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT05522660
Brief Title
Immunotherapy or Targeted Therapy With or Without Stereotactic Radiosurgery for Patients With Brain Metastases From Melanoma or Non-small Cell Lung Cancer
Acronym
USZ-STRIKE
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 30, 2022 (Actual)
Primary Completion Date
January 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ETOP IBCSG Partners Foundation
Collaborators
USZ Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer, Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
190 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
standard systemic treatment with stereotactic radiosurgery (SRS)
Arm Type
Experimental
Arm Description
Arm A
Arm Title
standard systemic treatment without stereotactic radiosurgery
Arm Type
Active Comparator
Arm Description
Arm B
Intervention Type
Radiation
Intervention Name(s)
Stereotactic radiosurgery
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Immune checkpoint inhibitor
Other Intervention Name(s)
standard of care treatment
Intervention Description
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.
Primary Outcome Measure Information:
Title
CNS-specific PFS, locally assessed as per iRANO criteria
Description
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.
Time Frame
from date of randomization until the date of documented CNS-specific progression, assessed up to 42 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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). Age of 18 years or older Karnofsky performance status of 60 or more Life expectancy >12 weeks 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. 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. Written IC for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention. Exclusion Criteria: Confirmed or probable leptomeningeal metastasis according to EANO ESMO criteria1 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. Prior whole brain irradiation or focal radiation therapy to the brain Prior systemic treatment for brain metastases Contra-indication for SRS For patients with NSCLC: any previous anticancer systemic therapy other than those under investigation in this study. 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. Women who are pregnant or in the period of lactation. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Heidi Roschitzki-Voser, Dr.
Phone
+41 31 511 94 18
Email
heidi.roschitzki@etop.ibcsg.org
First Name & Middle Initial & Last Name or Official Title & Degree
Susanne Roux
Phone
+41 31 511 94 17
Email
susanne.roux@etop.ibcsg.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Weller, MD
Organizational Affiliation
University of Zurich
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Rolf Stahel, MD
Organizational Affiliation
ETOP IBCSG Partners Foundation
Official's Role
Study Chair
Facility Information:
Facility Name
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
City
Napoli
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paolo Ascierto
Email
p.ascierto@istitutotumori.na.it
Facility Name
Santa Maria della Misericordia Hospital
City
Perugia
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mario Mandala
Email
mario.mandala@unipg.it
Facility Name
Istituto Nazionale Tumori "Regina Elena"
City
Roma
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabriele Minuti
Email
gabriele.minuti@ifo.it
Facility Name
Policlinico Umberto 1
City
Rome
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giuseppe Minniti
Email
giuseppe.minniti@uniroma1.it
Facility Name
Azienda ospedaliero-universitaria Senese Siena
City
Siena
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Maria di Giacomo
Email
a.m.digiacomo@ao-siena.toscana.it
Facility Name
NKI-AVL
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul Baas
Email
p.baas@nki.nl
Facility Name
Inselspital
City
Bern
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ekin Ermis
Email
ekin.ermis@insel.ch
Facility Name
Kantonsspital Winterthur
City
Winterthur
Country
Switzerland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Natalie Fischer
Email
natalie.fischer@ksw.ch
Facility Name
Universitätsspital Zürich
City
Zürich
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Weller, Prof.
Email
Michael.Weller@usz.ch
Facility Name
Royal Marsden (Sutton)
City
London
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mary O'Brian
Email
mary.obrien@rmh.nhs.uk
Facility Name
Christie NHS Manchester
City
Manchester
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Hughes
Email
sarah.hughes91@nhs.net

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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