Brigatinib Post Definitive Chemo-radiotherapy in Patients with ALK-fusion Non-small Cell Lung Cancer
- Conditions
- ALK-rearrangementNSCLC, Stage III
- Interventions
- Registration Number
- NCT05718297
- Lead Sponsor
- ETOP IBCSG Partners Foundation
- Brief Summary
BOUNCE is an international multicentre randomised phase II trial. The trial treatment consists of brigatinib 180 mg once daily p.o., with seven day lead-in at 90 mg once daily, for 3 years or until progression of disease. The primary objective of this trial is to evaluate the efficacy in terms of progression-free survival (PFS) for brigatinib consolidation, compared to observation/durvalumab, in patients with unresectable stage III NSCLC and ALK-rearrangement who completed definitive chemo-radiotherapy without disease progression.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- 44
Inclusion criteria for enrolment
- Pathologically documented, treatment naïve unresectable stage III NSCLC
- Documented ALK-fusion, tested locally on tumour tissue by a validated method (DNA NGS, RNA NGS, FISH, IHC, or ctDNA)
- ECOG Performance Status 0-1
- Age ≥18 years
- Patient is a candidate to receive chemo-radiotherapy, as per investigator's assessment (including adequate haematological, renal and liver function as per local guidelines).
- 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 5 weeks before enrolment.
- Ability to comply with the trial protocol, in the investigator's judgment.
- Written IC for trial participation must be signed and dated by the patient and the investigator prior to any trial-related intervention, including the submission of mandatory biomaterial.
Eligibility criteria for randomisation Randomisation of eligible patients must occur within 8 weeks after the last radiotherapy fraction.
- Completion of thoracic radiotherapy
- Non-PD at restaging
- Adequate haematological function
- Adequate renal function
- Adequate liver and pancreatic function
- 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 before randomisation and should be repeated within 3 days before the first dose of brigatinib.
- No radiation-pneumonitis of grade ≥2
- All other AEs from previous chemo-radiotherapy resolved to grade <2 (except for alopecia)
- ECOG 0-2
- No major surgery as defined by the investigator within 4 weeks of the the first planned dose of brigatinib.
Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.
- No systemic treatment with strong cytochrome p-450 (cyp)3a inhibitors, strong cyp3a inducers, or moderate cyp3a inducers within 14 days before randomisation.
- Diagnosis of another primary malignancy other than NSCLC. With the exception of adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years since the diagnosis of the other primary malignancy.
- Prior treatment for NSCLC
- Any evidence of stage IV NSCLC
- Significant, uncontrolled, or active cardiovascular disease
- Uncontrolled hypertension Patients with hypertension should be under treatment on study entry to control blood pressure.
- History or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis.
- Ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics.
- Malabsorption syndrome or other GI illness that could affect oral absorption of brigatinib.
- Known or suspected hypersensitivity to brigatinib or its excipients.
- Any concurrent medical condition which, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of brigatinib.
- 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 trial until at least 4 months after the last dose of protocol treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental arm Brigatinib Brigatinib 180 mg once daily p.o., with seven day lead-in at 90 mg once daily, for 3 years or until progression of disease, or unacceptable toxicities or withdrawal of consent Control arm Durvalumab Patients in the control arm will be observational, or, as per investigators choice, patients may receive durvalumab, administered within the label in the respective country.
- Primary Outcome Measures
Name Time Method Progression-free survival, according to RECIST v1.1, evaluated in the ITT cohort. PFS will be compared between the two arms. From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient) defined as the time from the date of randomisation until documented progression (according to RECIST v1.1) or death, if progression is not documented
- Secondary Outcome Measures
Name Time Method Overall survival From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient) Defined as the time from the date of randomisation until death from any cause
Toxicity according to CTCAE v5.0 From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient) All safety parameters from enrolment will be summarised in tables to evaluate the toxicity/safety profile of the protocol treatment based on:
* Adverse events according to CTCAE v5.0 (any-cause as well as treatment-related) including adverse events leading to dose interruptions, withdrawal of protocol treatment, and death
* Severe, serious, and selected adverse events
* Deaths
* Laboratory parameters and abnormalities, and vital signs.CNS-relapse-free survival From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient) Defined as the time from the date of randomisation until documented CNS-relapse, at the first disease progression, according to RECIST v1.1 or death from any cause, if CNS-relapse is not documented
Patterns of disease progression From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient) Defined as the site of first progression after randomisation: None, locoregional, distant (bone, brain, liver, etc.) or both locoregional and distant.
Trial Locations
- Locations (20)
CHU Angers
🇫🇷Angers, France
Caen - CHU
🇫🇷Caen, France
Hôpital de Marseille
🇫🇷Marseille, France
IRCCS Instituto Tumori Giovanni Paolo II
🇮🇹Bari, Italy
IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
🇮🇹Meldola, Italy
AOU Maggiore della Carità
🇮🇹Novara, Italy
Fondazione IRCCS Policlinico S. Matteo
🇮🇹Pavia, Italy
Santa Maria della Misericordia Hospital
🇮🇹Perugia, Italy
AULSS2 Marca Trevigiana Treviso
🇮🇹Treviso, Italy
Universita di Verona - Department of Medicine
🇮🇹Verona, Italy
Medical University Gdansk
🇵🇱Gdańsk, Poland
Hospital Universitario Dr Balmis Alicante - ISABIAL
🇪🇸Alicante, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Basurto
🇪🇸Bilbao, Spain
Hospital Universitario de Jerez de la Frontera
🇪🇸Jerez De La Frontera, Spain
Hospital Universitario Lucus Augusti
🇪🇸Lugo, Spain
H. Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Spain
Royal Marsden Hospital (Fulham Road)
🇬🇧London, United Kingdom
Royal Marsden Hospital (Sutton)
🇬🇧London, United Kingdom