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

NCT05718297 | Withdrawn Phase 2 DMC

• 1 other identifier: ETOP 21-21
• Study Type: interventional
• Target: N/A
• Locations: 5 countries
• Sites: 20

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

Outcome Measures

Primary Outcomes (1)

• Progression-free survival, according to RECIST v1.1, evaluated in the ITT cohort. PFS will be compared between the two arms.

  defined as the time from the date of randomisation until documented progression (according to RECIST v1.1) or death, if progression is not documented

  From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)

Secondary Outcomes (4)

• Overall survival

  From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)

• CNS-relapse-free survival

  From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)

• Patterns of disease progression

  From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)

• 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)

Study Arms (2)

Experimental arm

EXPERIMENTAL

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

Drug: Brigatinib

Control arm

ACTIVE COMPARATOR

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.

Drug: Durvalumab

Interventions

Brigatinib 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.

Experimental arm

Durvalumab 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.

Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Takeda: collaborator

Study Sites (20)

CHU Angers

Angers, France

Location

Caen - CHU

Caen, France

Location

Hôpital de Marseille

Marseille, France

Location

IRCCS Instituto Tumori Giovanni Paolo II

Bari, Italy

Location

IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)

Meldola, Italy

Location

AOU Maggiore della Carità

Novara, Italy

Location

Fondazione IRCCS Policlinico S. Matteo

Pavia, Italy

Location

Santa Maria della Misericordia Hospital

Perugia, Italy

Location

AULSS2 Marca Trevigiana Treviso

Treviso, Italy

Location

Universita di Verona - Department of Medicine

Verona, Italy

Location

Medical University Gdansk

Gdansk, Poland

Location

Hospital Universitario Dr Balmis Alicante - ISABIAL

Alicante, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario Basurto

Bilbao, Spain

Location

Hospital Universitario de Jerez de la Frontera

Jerez de la Frontera, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, Spain

Location

H. Puerta de Hierro Majadahonda

Majadahonda, Spain

Location

Royal Marsden Hospital (Fulham Road)

London, United Kingdom

Location

Royal Marsden Hospital (Sutton)

London, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

brigatinib; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Rafal Dziadziuszko, MD

  Dept. of Oncology and Radiotherapy, Medical University of Gdansk

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 8, 2023
• Study Start: June 7, 2024
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: October 8, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

ES (7); IT (7); FR (3); GB (2); PL (1)