NSCLC, Stage IIIPhase 2BOUNCENCT05718297
Brigatinib Post Definitive Chemo-radiotherapy in Patients with ALK-fusion Non-small Cell Lung Cancer
A Phase 2 study testing Brigatinib and Durvalumab in people with NSCLC, Stage III and ALK-rearrangement, run by ETOP IBCSG Partners Foundation at 20 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC, Stage III, ALK-rearrangement
- What is being tested?
- Brigatinib and Durvalumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 20 sitesin 5 countries
- Study dates
- 7 Jun 2024to 30 Sep 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
20 sites in 5 countries.
20 sites in 5 countries
Italy7 sites
IRCCS Instituto Tumori Giovanni Paolo II
Bari
IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
Meldola
AOU Maggiore della Carità
Novara
Fondazione IRCCS Policlinico S. Matteo
Pavia
Santa Maria della Misericordia Hospital
Perugia
AULSS2 Marca Trevigiana Treviso
Treviso
Universita di Verona - Department of Medicine
Verona
Spain7 sites
Hospital Universitario Dr Balmis Alicante - ISABIAL
Alicante
Hospital de la Santa Creu i Sant Pau
Barcelona
Hospital Vall d'Hebron
Barcelona
Hospital Universitario Basurto
Bilbao
Hospital Universitario de Jerez de la Frontera
Jerez de la Frontera
Hospital Universitario Lucus Augusti
Lugo
H. Puerta de Hierro Majadahonda
Majadahonda
United Kingdom2 sites
Royal Marsden Hospital (Fulham Road)
London
Royal Marsden Hospital (Sutton)
London
About this study
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
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
- Being tested
- Brigatinib, Durvalumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrigatinibDrug
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.
DurvalumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
Secondary outcomes (4)
Overall survival
Defined as the time from the date of randomisation until death from any cause
Measured: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
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
Measured: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
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.
Measured: 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
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.
Measured: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2023
- Study start7 Jun 2024
- Primary completion30 Sep 2024
- Study completion30 Sep 2024
Why it stopped: Despite our efforts, the trial faced challenges like a longer activation period and slower accrual. We proposed a redesign, but TAKEDA withdrew. As a non-profit organisation, we can't continue without TAKEDA's support and must discontinue the trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLC, Stage IIIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- ETOP IBCSG Partners Foundation
- Sponsor type
- Research network
- Collaborators
- Takeda
- Responsible party
- Sponsor
- Investigators
- Rafal Dziadziuszko, MD, Study chair, Dept. of Oncology and Radiotherapy, Medical University of Gdansk
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05718297
- Sponsor's protocol ID
- ETOP 21-21
- Acronym
- BOUNCE
- Status last verified
- Oct 2024
- First submitted
- 30 Jan 2023
- Last updated
- 8 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05718297
- Acronym / sponsor ID
- BOUNCE / ETOP 21-21
- Conditions
- NSCLC, Stage III, ALK-rearrangement
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Despite our efforts, the trial faced challenges like a longer activation period and slower accrual. We proposed a redesign, but TAKEDA withdrew. As a non-profit organisation, we can't continue without TAKEDA's support and must discontinue the trial.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- ETOP IBCSG Partners FoundationResearch network
- Collaborators
- Takeda
- Study start
- 7 Jun 2024 (actual)
- Primary completion
- 30 Sep 2024 (actual)
- Study completion
- 30 Sep 2024 (actual)
- First posted
- 8 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Drug: BrigatinibBrigatinib 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 | Active comparator | Drug: DurvalumabPatients in the control arm will be observational, or, as per investigators choice, patients may receive durvalumab, administered within the label in the respective country. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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).
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BrigatinibBrigatinib 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. | Drug | Experimental arm |
| DurvalumabPatients 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 | Control arm |
Primary outcome
Progression-free survival, according to RECIST v1.1, evaluated in the ITT cohort. PFS will be compared between the two arms.
Time frame: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
defined as the time from the date of randomisation until documented progression (according to RECIST v1.1) or death, if progression is not documented
4 secondary outcomes
Overall survival
Time frame: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
CNS-relapse-free survival
Time frame: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
Patterns of disease progression
Time frame: 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
Time frame: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2024.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rafal Dziadziuszko, MD study chair
Dept. of Oncology and Radiotherapy, Medical University of Gdansk
20 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Brigatinib and Durvalumab in people with NSCLC, Stage III and ALK-rearrangement, run by ETOP IBCSG Partners Foundation at 20 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 8 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Italy, Spain, France, United Kingdom, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival, according to RECIST v1.1, evaluated in the ITT cohort. PFS will be compared between the two arms. (time frame: From the date of enrolment until last tumour assessment (approximately 45-48 months after enrolment of the first patient)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2024.