DETERMINE Trial Treatment Arm 06: Capmatinib in Adult Patients With Cancers Harbouring MET Dysregulations
NCT ID: NCT06988475
Last Updated: 2025-11-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE2/PHASE3
30 participants
INTERVENTIONAL
2024-11-19
2029-10-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Capmatinib works in patients with lung cancer with a particular mutation in their cancer known as a METex14 skipping mutation.
Investigators now wish to find out if it will be useful in treating patients with other cancer types which have the same mutation or other specific mutations or changes which take place in the MET gene. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future.
This trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
DETERMINE Trial Treatment Arm 01: Alectinib in Adult, Paediatric and Teenage/Young Adult Patients With ALK Positive Cancers
NCT05770037
DETERMINE Trial Treatment Arm 03: Entrectinib in Adult, Paediatric and Teenage/Young Adult Patients With ROS1 Gene Fusion-Positive Cancers.
NCT05770544
DETERMINE Trial Treatment Arm 02: Atezolizumab in Adult, Paediatric and Teenage/Young Adult Patients With Cancers With High Tumour Mutational Burden (TMB) or Microsatellite Instability-high (MSI-high) or Proven Constitutional Mismatch Repair Deficiency (CMMRD) Disposition
NCT05770102
Study of Capmatinib in Chinese Adult Patients With Advanced Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation
NCT04677595
A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer
NCT05488314
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
\*Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and teenagers/young adult cancers) or common cancers with rare alterations.
This treatment arm has a target sample size of 30 evaluable patients. Sub-cohorts may be defined and further expanded to a target of 30 evaluable patients each.
The ultimate aim is to translate positive clinical findings to the NHS (Cancer Drugs Fund) to provide new treatment options for rare adult cancers.
OUTLINE:
Pre-screening: The Molecular Tumour Board makes a treatment recommendation for the patient based on molecularly-defined cohorts (See information on Master Screening Protocol below).
Screening: Consenting patients undergo biopsy and collection of blood samples for research purposes.
Treatment: Patients will receive capmatinib until disease progression without clinical benefit, unacceptable adverse events (AEs) or withdrawal of consent. Patients will also undergo collection of blood samples at various intervals while receiving treatment and at End of Treatment (EoT).
After completion of study treatment, patients are followed up every 3 months for 2 years.
THE DETERMINE TRIAL MASTER (SCREENING) PROTOCOL:
Please see DETERMINE Trial Master (Screening) Protocol record (NCT05722886) for information on the DETERMINE Trial Master Protocol and applicable documents.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment Arm 06: Capmatinib
This capmatinib treatment arm is for adult partients with cancers harbouring MET dysregulations.
Capmatinib
Patients will be administered capmatinib orally at a daily dose of 800 mg consisting of 400 mg (two 200mg tablets) twice daily. Each cycle of treatment will consist of 28 days and patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Capmatinib
Patients will be administered capmatinib orally at a daily dose of 800 mg consisting of 400 mg (two 200mg tablets) twice daily. Each cycle of treatment will consist of 28 days and patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
B. Adult patients ≥18 years old.
C. Women of childbearing potential are eligible, provided that they meet the following criteria:
* Have a negative serum or urine pregnancy test before enrolment, and
* Agree to use one form of highly effective birth control method (a method that can achieve a failure rate of \<1% when used consistently and correctly), such as:
I. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation \[oral, intravaginal or transdermal\])
II. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
III. intrauterine device (IUD)
IV. Intrauterine hormone-releasing system (IUS)
V. bilateral tubal occlusion
VI. vasectomised partner
VII. sexual abstinence
Effective from the first administration of capmatinib, throughout the trial and for seven days after the last administration of capmatinib.
D. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from first administration of capmatinib, throughout the trial and for seven days after the last administration of capmatinib:
* Agree to take measures not to father children by using a barrier method of contraception (e.g. condom) or sexual abstinence.
* Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses a highly effective method of contraception, as in criterion C above.
* Male patients with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom) to prevent drug exposure of the foetus or neonate.
All male patients must refrain from donating sperm for the same period.
E. Patients must be able and willing to undergo a fresh biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and/or trephine or lymph node biopsy samples may be taken.
F. Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.
Exclusion Criteria
B. Prior treatment with a selective MET inhibitor or HGF-targeting therapy unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to capmatinib.
C. Carcinomatous meningitis.
D. Presence or history of additional malignant disease that has been diagnosed and/or required therapy within the past three years. Exceptions to this exclusion include: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
E. Presence or history of interstitial lung disease (ILD) and/or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention) and evidence of active pneumonitis on screening chest computed tomography (CT) scan. Prior localised radiotherapy related pneumonitis is permitted if resolved and off steroids and asymptomatic for at least six months.
F. Clinically significant, uncontrolled heart disease such as:
* Unstable angina within three months prior to screening
* Myocardial infarction within three months prior to screening
* History of documented congestive heart failure (New York Heart Association functional classification III-IV)
* Uncontrolled hypertension defined by a systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening.
Patients with a cerebrovascular event (including stroke or transient ischaemic attack \[TIA\]) within three months before screening.
• Patients with primary CNS tumours may be considered unless intra-tumoural bleeding has occurred within two weeks of the first dose of capmatinib, and patients with punctate CNS haemorrhages \<3 mm may be considered.
G. History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the trial such as:
* Concomitant clinically significant cardiac arrhythmias (atrial and ventricular), e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker
* History of familial long QT syndrome or known family history of Torsades de Pointes
* Resting QTcF (Corrected QT interval by Fridericia formula) ≥450 msec (male) or ≥460 msec (female) at screening ECG (as a mean of triplicate ECG)
H. Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within four weeks prior to starting trial treatment (two weeks for resection of brain lesions) or patients who have not recovered from side effects of such procedure. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and patients can be enrolled in the trial at least one week after the procedure.
I. Patients receiving treatment with strong inducers of cytochrome P450 (CYP) 3A that cannot be discontinued at least one week prior to the start of treatment with capmatinib and for the duration of the trial.
J. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial (including absorption of oral medications) that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.
K. Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the administration or absorption of capmatinib (e.g., Crohn's disease, ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome or short gut syndrome). Unable to swallow capmatinib intact, without chewing or crushing the tablets (as per the dosing schedule).
L. Active infections including, but not limited to, hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Screening for known chronic conditions is not required. Patients with known serological evidence of chronic HBV or HCV infection whose disease is controlled under antiviral therapy according to local regulation are eligible. Patients with history of testing positive for human immunodeficiency virus (HIV) infection are eligible provided the each of the following conditions are met:
* CD4 count ≥350/μL;
* undetectable viral load;
* receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and
* no HIV/ acquired immune deficiency syndrome-associated opportunistic infection in the last 12 months.
M. Known hypersensitivity to any of the excipients of capmatinib.
N. Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the two weeks prior to trial entry to manage CNS symptoms. Primary brain or CNS malignancies are allowed providing the patient is clinically stable (if corticosteroids are required, they must be at a stable or decreasing dose for at least 14 days prior to Cycle 1 Day 1). If patients are on corticosteroids for endocrine deficiencies or tumour-associated symptoms other than CNS related, the dose must have been stabilised (or decreasing) for at least five days before Cycle 1 Day 1.
O. Patients receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least one week before first dose of capmatinib, and for the duration of the trial. Patients on non-enzyme-inducing anticonvulsants are eligible.
P. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or for seven days following their last dose of capmatinib.
Q. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during capmatinib treatment or within six months after the final dose of capmatinib.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Birmingham
OTHER
Royal Marsden NHS Foundation Trust
OTHER
Novartis Pharmaceuticals
INDUSTRY
University of Manchester
OTHER
Cancer Research UK
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Matthew Krebs, Dr
Role: PRINCIPAL_INVESTIGATOR
The Christie Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Belfast City Hospital
Belfast, , United Kingdom
University Hospital Birmingham
Birmingham, , United Kingdom
Bristol Haematology and Oncology Centre
Bristol, , United Kingdom
Addenbrooke's Hospital
Cambridge, , United Kingdom
Velindre Cancer Centre
Cardiff, , United Kingdom
Western General Hospital
Edinburgh, , United Kingdom
The Beatson Hospital
Glasgow, , United Kingdom
Leicester Royal Infirmary
Leicester, , United Kingdom
University College London Hospital
London, , United Kingdom
Guy's Hospital
London, , United Kingdom
The Christie Hospital
Manchester, , United Kingdom
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, , United Kingdom
Freeman Hospital
Newcastle, , United Kingdom
Churchill Hospital
Oxford, , United Kingdom
Western Park Hospital
Sheffield, , United Kingdom
Southampton General Hospital
Southampton, , United Kingdom
Royal Marsden Hospital
Sutton, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Stefan Symeonides, Dr
Role: primary
Related Links
Access external resources that provide additional context or updates about the study.
Overview of the DETERMINE trial
ClinicalTrials.gov record for DETERMINE Trial Master Screening Protocol (NCT05722886).
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CRUKD/21/004 - Treatment Arm 6
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.