Brigatinib Post Definitive Chemo-radiotherapy in Patients with ALK-fusion Non-small Cell Lung Cancer

NCT ID: NCT05718297

Last Updated: 2024-10-08

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-07
• Study Completion Date: 2024-09-30

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.

Conditions

NSCLC, Stage III; ALK-rearrangement

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental arm

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

Group Type: EXPERIMENTAL

Brigatinib

Intervention Type: DRUG

Brigatinib is administered for 3 years or until progression of disease, or unacceptable toxicities or withdrawal of consent, whatever occurs first. After the treatment period of 3 years, patient's ongoing treatment will be managed according to local standard and best clinical practice.

Brigatinib should be taken approximately at the same time each day. It may be taken with or without food. Patients shall be instructed to swallow the tablets whole and not crush or chew them.

Control arm

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.

Group Type: ACTIVE_COMPARATOR

Durvalumab

Intervention Type: DRUG

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.

Interventions

Brigatinib

Brigatinib is administered for 3 years or until progression of disease, or unacceptable toxicities or withdrawal of consent, whatever occurs first. After the treatment period of 3 years, patient's ongoing treatment will be managed according to local standard and best clinical practice.

Brigatinib should be taken approximately at the same time each day. It may be taken with or without food. Patients shall be instructed to swallow the tablets whole and not crush or chew them.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rafal Dziadziuszko, MD

Role: STUDY_CHAIR

Dept. of Oncology and Radiotherapy, Medical University of Gdansk

Locations

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

Gdansk, , 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

Countries

France; Italy; Poland; Spain; United Kingdom

Other Identifiers

ETOP 21-21

Identifier Type: -

Identifier Source: org_study_id