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

NSCLC, Stage III Clinical Trial

— BOUNCE  

Official title:

A Multicentre, Randomised, Phase II Trial of Brigatinib Consolidation Versus Observation or Durvalumab in Patients With Unresectable Stage III NSCLC and ALK-rearrangement, After Definitive Chemo-radiotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05718297
• Other study ID #: ETOP 21-21
• Status: Recruiting
• Phase: Phase 2
• Start date: May 2024
• Est. completion date: April 2029

Study information

• Verified date: May 2024
• Source: ETOP IBCSG Partners Foundation
• Contact: Heidi Roschitzki, PhD
• Phone: +41 31 511 94 00
• Email: heidi.roschitzki[@]etop.ibcsg.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: April 2029
• Est. primary completion date: April 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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.

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.

Related Conditions & MeSH terms

• NSCLC, Stage III

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	Caen - CHU	Caen
France	Hôpital de Marseille	Marseille
Italy	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
Poland	Medical University Gdansk	Gdansk
Spain	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
United Kingdom	Royal Marsden Hospital (Fulham Road)	London
United Kingdom	Royal Marsden Hospital (Sutton)	London

Sponsors (2)

Lead Sponsor	Collaborator
ETOP IBCSG Partners Foundation	Takeda

Countries where clinical trial is conducted

France,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival	Defined as the time from the date of randomisation until death from any cause	From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
Secondary	CNS-relapse-free survival	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	From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
Secondary	Patterns of disease progression	Defined as the site of first progression after randomisation: None, locoregional, distant (bone, brain, liver, etc.) or both locoregional and distant.	From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
Secondary	Toxicity according to CTCAE v5.0	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.	From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)