Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
55
Countries
4
Sites
18
Non-small cell lung cancer (NSCLC)
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. Secon…
Key facts
- Sponsor
- ETOP IBCSG Partners Foundation
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Neoplasms [C04]
- Trial duration
- 22 Feb 2024 → 30 Sep 2024
- Decision date (initial)
- 2023-11-10
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Takeda Development Center Americas, Inc
External identifiers
- EU CT number
- 2022-502467-38-00
- ClinicalTrials.gov
- NCT05718297
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Safety, Efficacy
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. Secondary measures of clinical efficacy will be evaluated, including overall survival (OS), CNS-relapse-free survival, patterns of disease progression, and safety.
Secondary objectives 1
- To evaluate secondary measures of clinical efficacy including overall survival (OS), CNS-relapse-free survival, patterns of disease progression, and safety.
Conditions and MedDRA coding
Non-small cell lung cancer (NSCLC)
Study design 6 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Screening The following examinations have to be done within 5 weeks before enrolment:
Written informed consent
Written informed consent (signed and dated by patient and investigator) must be obtained before any trial-specific evaluations and interventions, including the collection of mandatory biological material. (Informed consent may be obtained earlier than 5 weeks before enrolment).
Eligibility for enrolment
All eligibility criteria listed must be met before enrolling the patient.
Demographics
Year of birth, gender, race.
Medical history
Smoking history, comorbidities (including COVID-19 infection), medications (including SARS-CoV-2 vaccination), allergies and baseline symptoms.
Physical examination
Including ECOG PS, blood pressure, heart rate, body temperature, body weight and height.
Pregnancy test
Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine beta HCG pregnancy test at screening before enrolment.
Pregnancy testing should be repeated for the duration of protocol treatment, if required per local laws and local clinical practice.
Routine laboratory assessments as per local clinical practice.
Radiological tumour assessment
• Brain imaging by MRI (preferable) or high-resolution brain CT
• Whole body FDG-PET-CT
TNM categories (for staging)
ALK-positivity on tumour tissue, assessed locally
FFPE tumour material for translational research
Blood samples for translational research
|
Not Applicable | None | ||
| 2 | Chemo-radiotherapy phase • Standard platinum-based chemotherapy to be administered as per local standards according to the ESMO guidelines.
• Radiotherapy defined with biologically equivalent dose of 54 – 66Gy
- concurrent or sequential to standard platinum-based chemotherapy
- or, exceptionally, curative radiotherapy alone
|
Not Applicable | None | ||
| 3 | Restaging The following assessments will be performed:
Brain imaging by MRI
Contrast-enhanced CT of thorax and upper abdomen
|
Not Applicable | None | ||
| 4 | Consolidation phase • 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.
• 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.
|
Randomised Controlled | None | 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 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. |
|
| 5 | Follow-up before progression Patients in the experimental arm and patients in the observation arm, who had the End of Treatment visit before progression, should have the following examinations documented every 12 weeks (±2 weeks, at about the same time as tumour imaging visits), from the end of treatment visit until documented progression of disease.
Physical examination
Including ECOG PS, blood pressure, heart rate, body temperature and body weight.
Radiological tumour assessment
• Brain imaging: by MRI (preferable) or high-resolution brain CT,
every 12 weeks (±2 weeks), until progression.
• Contrast-enhanced CT of thorax and upper abdomen, every 12 weeks (±2 weeks), until progression.
|
Not Applicable | None | ||
| 6 | Follow-up beyond progression After progression, all patients will be followed up every 12 weeks (±2 weeks) starting from date of progression until the trial ends. Upon upfront notification to ETOP IBCSG Partners, these visits can be done remotely over the phone.
The following should be documented:
Further lines of treatment
Survival
|
Not Applicable | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Most important inclusion criteria for enrolment: • Pathologically documented, treatment naïve unresectable stage III NSCLC • Documented ALK-fusion, tested locally on tumor 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 clinical practice). • Negative pregnancy test for women of childbearing potential. • Ability to comply with the trial protocol, in the investigator's judgment. • Written informed consent 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. Most important inclusion 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, renal and liver function. • Negative pregnancy test for women of childbearing potential • 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 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 1
- Most important exclusion criteria for enrolment: • Diagnosis of another primary malignancy other than NSCLC. • Prior treatment for NSCLC • Any evidence of stage IV NSCLC • Significant, uncontrolled, or active cardiovascular disease - History of clinically significant atrial arrhythmia (including clinically significant brady-arrhythmia), as determined by the treating physician. - Any history of clinically significant ventricular arrhythmia. - Cerebrovascular accident or transient ischemic attack within 6 months before enrolment. - Myocardial infarction within 6 months before enrolment. - Unstable angina within 6 months before enrolment. - Congestive heart failure within 6 months before enrolment. • 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 evaluations of brigatinib.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Progression-free survival, according to RECIST v1.1, evaluated in the ITT cohort. PFS will be compared between the two arms.
Secondary endpoints 4
- Overall survival
- CNS-relapse-free survival
- Patterns of disease progression
- Toxicity according to CTCAE v5.0
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
PRD10066549 · Product
- Active substance
- Brigatinib
- Other product name
- AP26113
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 90 mg milligram(s)
- Max total dose
- 630 mg milligram(s)
- Max treatment duration
- 7 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- TAKEDA DEVELOPMENT CENTER AMERICAS, INC.,
- Paediatric formulation
- No
- Orphan designation
- No
PRD10069416 · Product
- Active substance
- Brigatinib
- Other product name
- AP26113
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 180 mg milligram(s)
- Max total dose
- 27900 mg milligram(s)
- Max treatment duration
- 155 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- TAKEDA DEVELOPMENT CENTER AMERICAS, INC.,
- Paediatric formulation
- No
- Orphan designation
- No
Comparator 2
IMFINZI 50 mg/mL concentrate for solution for infusion.
PRD6651398 · Product
- Active substance
- Durvalumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Max daily dose
- 1500 mg milligram(s)
- Max total dose
- 60000 mg milligram(s)
- Max treatment duration
- 156 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XC28 — -
- Marketing authorisation
- EU/1/18/1322/001
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
IMFINZI 50 mg/mL concentrate for solution for infusion.
PRD6651400 · Product
- Active substance
- Durvalumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Max daily dose
- 1500 mg milligram(s)
- Max total dose
- 60000 mg milligram(s)
- Max treatment duration
- 156 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XC28 — -
- Marketing authorisation
- EU/1/18/1322/002
- MA holder
- ASTRAZENECA AB
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
ETOP IBCSG Partners Foundation
- Sponsor organisation
- ETOP IBCSG Partners Foundation
- Address
- Effingerstrasse 33
- City
- Bern
- Postcode
- 3008
- Country
- Switzerland
Scientific contact point
- Organisation
- ETOP IBCSG Partners Foundation
- Contact name
- ETOP IBCSG Partners Regulatory Office
Public contact point
- Organisation
- ETOP IBCSG Partners Foundation
- Contact name
- ETOP IBCSG Partners Regulatory Office
Third parties 3
| Organisation | City, country | Duties |
|---|---|---|
| Frontier Science Foundation-Hellas ORG-100047506
|
Athens, Greece | Code 10, Code 11 |
| Fisher Clinical Services GmbH ORG-100017323
|
Weil Am Rhein, Germany | Other |
| Centre Hospitalier Universitaire Vaudois ORG-100025536
|
Lausanne, Switzerland | Laboratory analysis |
Locations
4 EU/EEA countries · 18 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ended | 5 | 3 |
| Italy | Ended | 6 | 7 |
| Poland | Ended | 18 | 1 |
| Spain | Ended | 12 | 7 |
| Rest of world
United Kingdom, Switzerland
|
— | 14 | — |
Investigational sites
Centre Hospitalier Universitaire De Caen Normandie
Medical Oncology, Avenue De La Cote De Nacre, Cs 30001, Caen Cedex 9
Centre Hospitalier Universitaire D Angers
Medical Oncology, 4 Rue Larrey, 49933, Angers Cedex 9
Assistance Publique Hopitaux De Marseille
Medical Oncology, 265 Chemin Des Bourrely, 13015, Marseille
Azienda Ospedaliera Universitaria Integrata Verona
Medical Oncology, Piazzale Aristide Stefani 1, 37126, Verona
Azienda Unita' Locale Socio Sanitaria N. 2 Marca Trevigiana
Medical Oncology, Borgo Cavalli 42, 31100, Treviso
Hospital Santa Maria Della Misericordia
Medical Oncology, Piazzale Giorgio Menghini 1, 06129, Perugia
Istituto Tumori Bari Giovanni Paolo II
Medical Oncology, Viale Orazio Flacco 65, 70124, Bari
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Medical Oncology, Via Piero Maroncelli 40, 47014, Meldola
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Medical Oncology, Corso Giuseppe Mazzini 18, 28100, Novara
Fondazione IRCCS Policlinico San Matteo
Medical Oncology, Viale Camillo Golgi 19, 27100, Pavia
Uniwersyteckie Centrum Kliniczne
Medical Oncology, Ul. Mariana Smoluchowskiego 17, 80-214, Gdansk
Hospital Universitario Puerta De Hierro De Majadahonda
Medical Oncology, Calle De Manuel De Falla 1, 28222, Majadahonda
Hospital Universitari Vall D Hebron
Medical Oncology, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona
Hospital General Universitario Dr. Balmis
Medical Oncology, Avda. Pintor Baeza, s/n - 7ªC, Alicante
Hospital Universitario Lucus Augusti
Medical Oncology, Calle Ulises Romero 1, 27003, Lugo
Hospital De La Santa Creu I Sant Pau
Medical Oncology, Calle De San Antonio Maria Claret 167, 08025, Barcelona
Hospital Universitario Basurto
Medical Oncology, Montevideo Etorbidea 16-18, 48013, Bilbao
Hospital De Jerez De La Frontera
Medical Oncology, Carretera De La Ronda Circunvalacion S/n, 11408, Jerez De La Frontera
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2024-02-22 | ||||
| Italy | 2024-03-07 | 2024-06-07 | |||
| Spain | 2024-04-16 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| BOUNCE - No summary of results SUM-89041
|
2025-07-03T08:19:50 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| BOUNCE - No laypersons summary of results | 2025-07-03T08:20:16 | Submitted | Laypersons Summary of Results |
Documents 2 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | BOUNCE - No laypersons summary of results | 1 |
| Summary of results (for publication) | BOUNCE - No summary of results | 1 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-07-19 | Italy | Acceptable 2023-11-06
|
2023-11-10 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-04-17 | Italy | Acceptable 2024-07-22
|
2024-07-23 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-08-05 | Italy | Acceptable 2024-07-22
|
2024-08-05 |