Precision cancer medicine in hard-to-treat rare cancers - repurposing drugs in earlier lines of treatment - MATRIX-RARE.

Phase 2

Recruiting

• Conditions: Cancer

• Registration Number: 2024-513779-42-02
• Lead Sponsor: Oslo University Hospital HF

Brief Summary

• To describe the anti-tumour activity of commercially available targeted anti-cancer drugs used for treatment of patients with rare and hard to treat cancers.

• To describe serious toxicity related to the study treatment.

Detailed Description

All patients will have the tumour cells diagnosed with a large genepanel, analyzing more than 500 genes on DNA / RNA level. Patients will be treated based on the molecular characteristics of the tumor cells.

Study Timeline

• Study First Posted: 2025-02-12
• Last Update Posted: 2025-05-30

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 100

Inclusion Criteria

1. ECOG performance status 0-2

2. For orally administered drugs, the patient must have no known malabsorption syndrome

3. 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

4. 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

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.

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.

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”.

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.

2. Life expectancy minimum 3 months.

3. Age >17 years

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).

5. The patient has a rare cancer, defined as having an incidence of <6 / 100 000 / year.

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

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.

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.

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

Exclusion Criteria

1. MOLECULAR PROFILINGPatients with the following pre-existing cardiac conditions: uncontrolled angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure.

2. Patients with known allergy/hypersensitivity to the study drug (active substance or to any of the excipients).

3. Patients with acute gastrointestinal bleeding within 1 month of start of treatment

4. Patients with stroke (including TIA) or acute myocardial infarction within 4 months before the first dose of study treatment

5. Previous treatment with the selected study drug for the same malignancy.

6. 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.

7. Female patients who are pregnant or nursing

8. Patients who do not meet drug-specific eligibility requirements for the drug selected by the investigator.

9. Age < 18 years

10. Patients with left ventricular ejection fraction (LVEF) known to be < 40%.

11. Patients 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.

TREATMENT PHASE: 4. Patients 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).

5. Ongoing 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
1) Disease control (objective complete or partial response or stable disease) at 16 weeks after treatment initiation according to established response criteria		1) Disease control (objective complete or partial response or stable disease) at 16 weeks after treatment initiation according to established response criteria
2) Treatment-related grade ≥3 and serious adverse events for all cohorts.		2) Treatment-related grade ≥3 and serious adverse events for all cohorts.
3. Treatment-related grade 1-5 adverse events for cohorts with new treatment combinations		3. Treatment-related grade 1-5 adverse events for cohorts with new treatment combinations

Secondary Outcome Measures

Name	Time	Method
1) Progression-free survival		1) Progression-free survival
2) Overall survival		2) Overall survival
Duration of time on drug		Duration of time on drug

Trial Locations

Locations (15)

Nordlandssykehuset HF; 🇳🇴 Bodo, Norway

Stavanger University Hospital HF; 🇳🇴 Stavanger, Norway

Oslo University Hospital HF; 🇳🇴 Oslo, Norway

Helse Fonna HF; 🇳🇴 Haugesund, Norway

Sykehuset Telemark HF; 🇳🇴 Skien, Norway

Vestfold Hospital Trust; 🇳🇴 Tønsberg, Norway

Sorlandet Sykehus HF; 🇳🇴 Kristiansand S, Norway

Sykehuset Innlandet HF; 🇳🇴 Brumunddal, Norway

Helse Bergen HF; 🇳🇴 Bergen, Norway

Universitetssykehuset Nord-Norge HF; 🇳🇴 Tromsoe, Norway

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Nordlandssykehuset HF

🇳🇴Bodo, Norway

Bård Mannsåker

Site contact

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postmottak@nordlandssykehuset.no