Clinical trial NCT05718297: Brigatinib Post Definitive Chemo-radiotherapy in Patients with ALK-fusion Non-small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: NSCLC, Stage III
ALK-rearrangement
Lead sponsor: ETOP IBCSG Partners Foundation
Sponsor class: NETWORK
Collaborators: name: Takeda
First posted: 2023-02-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival, according to RECIST v1.1, evaluated in the ITT cohort. PFS will be compared between the two arms.
timeFrame: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
Secondary outcomes:
measure: Overall survival
timeFrame: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
measure: CNS-relapse-free survival
timeFrame: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
measure: Patterns of disease progression
timeFrame: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
measure: Toxicity according to CTCAE v5.0
timeFrame: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Caen
country: France
facility: Caen - CHU
city: Marseille
country: France
facility: Hôpital de Marseille
city: Bari
country: Italy
facility: IRCCS Instituto Tumori Giovanni Paolo II
city: Meldola
country: Italy
facility: IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
city: Novara
country: Italy
facility: AOU Maggiore della Carità
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico S. Matteo
city: Perugia
country: Italy
facility: Santa Maria della Misericordia Hospital
city: Treviso
country: Italy
facility: AULSS2 Marca Trevigiana Treviso
city: Verona
country: Italy
facility: Universita di Verona - Department of Medicine
city: Gdańsk
country: Poland
facility: Medical University Gdansk
city: Alicante
country: Spain
facility: Hospital Universitario Dr Balmis Alicante - ISABIAL
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Bilbao
country: Spain
facility: Hospital Universitario Basurto
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario de Jerez de la Frontera
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Majadahonda
country: Spain
facility: H. Puerta de Hierro Majadahonda
city: London
country: United Kingdom
facility: Royal Marsden Hospital (Fulham Road)
city: London
country: United Kingdom
facility: Royal Marsden Hospital (Sutton)
Study officials:
affiliation: Dept. of Oncology and Radiotherapy, Medical University of Gdansk
name: Rafal Dziadziuszko, MD
role: STUDY_CHAIR
References: