DABRAFENIB for Cancer|Rare cancer

Inclusion criteria

• {"criterion_text":"-1.\tECOG performance status 0-2"}
• {"criterion_text":"-2. Life expectancy minimum 3 months."}
• {"criterion_text":"-3. Age >17 years"}
• {"criterion_text":"-4. Patients must have evaluable disease. The exception is when the treatment is after radiotherapy e.g. in newly diagnosed glioblastoma. RECIST v1.1 (18, 25) will be used for patients with solid tumours(26)(27)(27). For glioblastoma patients, RANO 2.0 criteria will be used (28). iRECIST will be used for immunotherapy-cohorts (25)."}
• {"criterion_text":"-5. The patient has a rare cancer, defined as having an incidence of <6 / 100 000 / year."}
• {"criterion_text":"-6. The patient has an advanced cancer without effective treatment options according to ESMO-magnitude of clinical benefit scale (<4),. If the ESMO-MCBS is 3, and the prognosis on standard treatment is poor (median OS <2 years), the patient can be eligible (See also chapter 5).Informed Consent"}
• {"criterion_text":"-7. Ability to understand and the willingness to sign a written informed consent/assent document for molecular profiling as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol."}
• {"criterion_text":"-8. Type of Participant and Health status 8. Patient with a pathology-proven locally advanced or metastatic malignant disease with no efficient standard anti-cancer treatment or for whom, in the opinion of the investigator, no such treatment is available or indicated. The treatment can be administered in combination with radiation therapy, for example in patients with newly-diagnosed glioblastoma study treatment will be administered as add-on to standard treatment with radiotherapy and temozolomide. For patients with MGMT promoter methylation negative glioblastoma adjuvant temozolomide will be considered abandoned."}
• {"criterion_text":"-9. Patients must have acceptable organ function as defined below: a) Absolute neutrophil count ≥ 1.5 x109 / L b) Hemoglobin > 9 g/dl c) Platelets > 75,000/μl d) Total bilirubin < 1.5 x institutional upper limit of normal (ULN) e) AST (SGOT) and ALT(SGPT) < 2.5 x institutional upper limit of normal (ULN) (or < 5 x ULN in patients with known hepatic metastases) f) Calculated or measured creatinine clearance ≥ 40 mL/min/1.73 m2"}
• {"criterion_text":"-10. For orally administered drugs, the patient must have no known malabsorption syndrome"}
• {"criterion_text":"-11. Results must be available from a diagnostic test performed in a preapproved laboratory. The test used to qualify a patient for participation in MATRIX-RARE may have been performed on any specimen of the patient’s tumour obtained at any point during the patient’s care at the discretion of the patient’s treating physician. Genomic assays performed on cell-free DNA in plasma (“liquid biopsies”) will also be acceptable if the genomic analysis is performed. NGS analyses will be performed on a newly sampled biopsy if possible. Information from these analyses may be used upon progression, for evaluation of possible new cohort-inclusion"}
• {"criterion_text":"-12. Have a genomic profile for which treatment with one of the approved targeted anti-cancer therapies included in this study has potential clinical benefit see Section 3.3.4"}
• {"criterion_text":"-13. Sex and Contraceptive/Barrier Requirements 13. Because of the risks of drug treatment to the developing fetus, women of child-bearing potential and men must agree to use adequate highly effective methods of contraception for the duration of study participation, and for 4 to 24 months following completion of study therapy as defined in Section 11.4."}
• {"criterion_text":"-14. Women of child-bearing potential must have a negative highly sensitive pregnancy test no more than 72 h before treatment start, then monthly as long as contraception is required."}
• {"criterion_text":"-15. Male patients should avoid impregnating a female partner. Male study patients must agree to one of the following: practice effective barrier contraception as described under section 10.4 during the entire study treatment period and through a certain time after the last dose of study drug. Details are given in the “Drug specific amendment”."}
• {"criterion_text":"-16. Informed Consent 16. Ability to understand and the willingness to sign a written informed consent/assent document for treatment as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol."}

Exclusion criteria

• {"criterion_text":"-1.\tMOLECULAR PROFILINGPatients with the following pre-existing cardiac conditions: uncontrolled angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure."}
• {"criterion_text":"-6.\tPatients with known allergy/hypersensitivity to the study drug (active substance or to any of the excipients)."}
• {"criterion_text":"-7.\tPatients with acute gastrointestinal bleeding within 1 month of start of treatment"}
• {"criterion_text":"-8.\tPatients with stroke (including TIA) or acute myocardial infarction within 4 months before the first dose of study treatment"}
• {"criterion_text":"-9.\tPrevious treatment with the selected study drug for the same malignancy."}
• {"criterion_text":"-10. If the patient’s tumour has a genomic variant known to confer resistance to an anti-cancer agent available in this study, the patient will not be eligible to receive that agent but will be eligible to receive other drugs available in this study if all inclusion and exclusion criteria are met for that drug."}
• {"criterion_text":"-11. Female patients who are pregnant or nursing"}
• {"criterion_text":"-12. Patients who do not meet drug-specific eligibility requirements for the drug selected by the investigator."}
• {"criterion_text":"-13. Age < 18 years"}
• {"criterion_text":"-2.\tPatients with left ventricular ejection fraction (LVEF) known to be < 40%."}
• {"criterion_text":"-3.\tPatients with any other clinically significant medical condition which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, severe psychiatric illness situations, or anticipated or planned anti-cancer treatment or surgery."}
• {"criterion_text":"-TREATMENT PHASE: 4.\tPatients eligible to enter other ongoing trials which have the potential to benefit the patients equally or more than MATRIX-RARE, and for whom access to the ongoing trials is manageable (taking geography into consideration)."}
• {"criterion_text":"-5.\tOngoing toxicity > CTCAE grade 2, other than peripheral neuropathy, related to anti-tumour treatment that was completed within 4 weeks prior to treatment initiation. Patients with ongoing peripheral neuropathy of ≥ CTCAE grade 3."}

Primary endpoints

• {"endpoint_text":"-1) Disease control (objective complete or partial response or stable disease) at 16 weeks after treatment initiation according to established response criteria","definition_or_measurement_approach":"Measured by established response criteria: RECIST v1.1 for solid tumours, RANO 2.0 for glioblastoma, and iRECIST for immunotherapy cohorts as applicable."}
• {"endpoint_text":"-2) Treatment-related grade ≥3 and serious adverse events for all cohorts.","definition_or_measurement_approach":"Reported adverse events graded by CTCAE (treatment-related grade ≥3 and serious adverse events)."}
• {"endpoint_text":"-3. Treatment-related grade 1-5 adverse events for cohorts with new treatment combinations","definition_or_measurement_approach":"Reported adverse events graded by CTCAE (all grades 1–5) for cohorts receiving new combinations."}

Secondary endpoints

• {"endpoint_text":"-1) Progression-free survival","definition_or_measurement_approach":"Progression-free survival measured from treatment start to disease progression or death, using the applicable response criteria (RECIST v1.1, RANO 2.0, iRECIST)."}
• {"endpoint_text":"-2) Overall survival","definition_or_measurement_approach":"Overall survival measured from treatment start to death from any cause."}
• {"endpoint_text":"-Duration of time on drug","definition_or_measurement_approach":"Measured as duration of treatment exposure (time on study drug until discontinuation)."}

Norway

Earliest CTIS Part Ii Submission Date

23-01-2025

Latest Decision Or Authorization Date

10-10-2025

Processing Time Days

260

Number Of Sites

16

Number Of Participants

100

Primary sponsor

Full Name

Oslo University Hospital HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway

Third parties

• {"country":"","full_name":"Matrix","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Industry Partners (currently Novartis)","duties_or_roles":"Monetary support","organisation_type":""}