Trial Title:
Immunotherapy or Targeted Therapy with or Without Stereotactic Radiosurgery for Patients with Brain Metastases from Melanoma or Non-small Cell Lung Cancer
NCT ID:
NCT05522660
Condition:
Non-Small Cell Lung Cancer
Melanoma
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Melanoma
Brain Neoplasms
Immune Checkpoint Inhibitors
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Stereotactic radiosurgery
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.
Arm group label:
standard systemic treatment with stereotactic radiosurgery (SRS)
Intervention type:
Drug
Intervention name:
Immune checkpoint inhibitor
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.
Arm group label:
standard systemic treatment with stereotactic radiosurgery (SRS)
Arm group label:
standard systemic treatment without stereotactic radiosurgery
Other name:
standard of care treatment
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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
Address:
City:
Napoli
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Paolo Ascierto
Email:
p.ascierto@istitutotumori.na.it
Facility:
Name:
Santa Maria della Misericordia Hospital
Address:
City:
Perugia
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Mario Mandala
Email:
mario.mandala@unipg.it
Facility:
Name:
Istituto Nazionale Tumori "Regina Elena"
Address:
City:
Roma
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Gabriele Minuti
Email:
gabriele.minuti@ifo.it
Facility:
Name:
Policlinico Umberto 1
Address:
City:
Rome
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Giuseppe Minniti
Email:
giuseppe.minniti@uniroma1.it
Facility:
Name:
Azienda ospedaliero-universitaria Senese Siena
Address:
City:
Siena
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Anna Maria di Giacomo
Email:
a.m.digiacomo@ao-siena.toscana.it
Facility:
Name:
NKI-AVL
Address:
City:
Amsterdam
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Paul Baas
Email:
p.baas@nki.nl
Facility:
Name:
Vall Hebron Institute of Oncology (VHIO)
Address:
City:
Barcelona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Patricia Irano
Email:
piranzo@vhio.net
Facility:
Name:
Hospital Puerta de Hierro
Address:
City:
Majadahonda
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Ana Collazo Lorduy
Email:
anaclorduy@gmail.com
Facility:
Name:
Hospital La Fe
Address:
City:
Valencia
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Oscar Jose Juan Vidal
Email:
juan_osc@gva.es
Facility:
Name:
Inselspital
Address:
City:
Bern
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Ekin Ermis
Email:
ekin.ermis@insel.ch
Facility:
Name:
Kantonsspital Winterthur
Address:
City:
Winterthur
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Natalie Fischer
Email:
natalie.fischer@ksw.ch
Facility:
Name:
Universitätsspital Zürich
Address:
City:
Zürich
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Michael Weller, Prof.
Email:
Michael.Weller@usz.ch
Facility:
Name:
Royal Marsden (Sutton)
Address:
City:
London
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Mary O'Brian
Email:
mary.obrien@rmh.nhs.uk
Facility:
Name:
Christie NHS Manchester
Address:
City:
Manchester
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Sarah Hughes
Email:
sarah.hughes91@nhs.net
Start date:
November 30, 2022
Completion date:
December 2026
Lead sponsor:
Agency:
ETOP IBCSG Partners Foundation
Agency class:
Other
Collaborator:
Agency:
USZ Foundation
Agency class:
Other
Source:
ETOP IBCSG Partners Foundation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05522660
