Trametinib for Metastatic malignancy | BRAF gene mutation (impaired kinase activity)

Inclusion criteria

• {"criterion_text":"- 1. Male or female patients aged ≥18 years without upper age limit;"}
• {"criterion_text":"- 10. Written informed consent obtained according to international guidelines and local laws"}
• {"criterion_text":"- 11. Ability to understand the nature of the trial and the trial related procedures and to comply with them"}
• {"criterion_text":"- 2. Metastatic malignancy"}
• {"criterion_text":"- 3. Progression after standard treatment"}
• {"criterion_text":"- 4. BRAF mutation with impaired kinase activity (according to Brummer laboratory at Medical Center – University of Freiburg)"}
• {"criterion_text":"- 5. BRAF mutation with sensitivity to sorafenib in vitro (according to Brummer laboratory at Medical Center – University of Freiburg)"}
• {"criterion_text":"- 6. At least one lesion that can be measured by CT, PET-CT, or MRI according to RECIST 1.1"}
• {"criterion_text":"- 7. Adequate hepatic function with • AST and ALT < 3 ULN AND • Total bilirubin < 1.5 x ULN. Patient with Gilberts syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible."}
• {"criterion_text":"- 8. Calculated creatinine clearance ≥ 50 mL/min by the Cockcroft-Gault- Equation"}
• {"criterion_text":"- 9. Patient is able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels"}

Exclusion criteria

• {"criterion_text":"- 1. Finding of a strongly activating BRAF mutation"}
• {"criterion_text":"- 18. Concurrent treatment with anticancer therapy (other than IMPs)"}
• {"criterion_text":"- 19. Concomitant use of strong Cytochrome P450 3A4 inducers"}
• {"criterion_text":"- 10. Patients who have received sorafenib in the past"}
• {"criterion_text":"- 20. For female patient: current or planned pregnancy, nursing period"}
• {"criterion_text":"- 21. Failure to use one of the following safe methods of contraception: hormonal contraception in combination with a mechanical method of contraception, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence"}
• {"criterion_text":"- 11. Patient with a known history of aneurysms"}
• {"criterion_text":"- 12. History of retinal vein occlusion (RVO)"}
• {"criterion_text":"- 13. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression"}
• {"criterion_text":"- 2. Life expectancy <3 months"}
• {"criterion_text":"- 3. Patients with hepatocellular carcinoma (HCC) or hepatic cirrhosis"}
• {"criterion_text":"- 6. Uncontrolled bacterial, viral or fungal infection"}
• {"criterion_text":"- 4. Patient with ECOG >2"}
• {"criterion_text":"- 5. Patients with known positivity for HIV, Hepatitis B or Hepatitis C at the time of screening"}
• {"criterion_text":"- Treatment with therapeutic anticoagulation or dual platelets inhibition"}
• {"criterion_text":"- 7. Radiation therapy, major surgery, other locoregional therapy, within 4 weeks prior to the first dose of study drug"}
• {"criterion_text":"- 8. Serious cardiovascular disease (e.g. manifest heart failure, coronary heart disease, uncontrolled hypertension)"}
• {"criterion_text":"- 9. Any serious disease interfering with a regular therapy according to the study protocol"}
• {"criterion_text":"- 14. Ongoing interstitial lung disease or pneumonitis, which requires treatment/medication"}
• {"criterion_text":"- 15. Known hypersensitivity to the active substances or any of the excipients"}
• {"criterion_text":"- 16. Participation in any other interventional clinical trial within the last 30 days before the start of this trial; simultaneous participation in registry and diagnostic trials is allowed"}
• {"criterion_text":"- 17. Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial;"}

Primary endpoints

• {"endpoint_text":"- MTD of trametinib given in combination with sorafenib","definition_or_measurement_approach":"Primary objective: is to determine the maximum tolerated dose (MTD) of trametinib combined with sorafenib and the recommended phase II dose (RP2D) for expansion part of the trial"}

Secondary endpoints

• {"endpoint_text":"- Adverse (AEs), serious adverse events (SAEs)","definition_or_measurement_approach":"Safety and tolerability monitoring of AEs and SAEs as standard safety reporting; specific collection/grading approach not detailed in the provided record"}
• {"endpoint_text":"- Disease control rate (SD, PR or CR according to RECIST 1.1), best response during trial treatment","definition_or_measurement_approach":"Assessment by RECIST 1.1 (stable disease, partial response, complete response); best overall response during treatment"}
• {"endpoint_text":"- Overall response rate (CR or PR according to RECIST 1.1) at the end of cycle 4 and cycle 7","definition_or_measurement_approach":"Response assessed per RECIST 1.1 at specified timepoints (end of cycle 4 and cycle 7)"}
• {"endpoint_text":"- Overall survival from start of trial treatment","definition_or_measurement_approach":"Overall survival measured from start of trial treatment to death from any cause"}
• {"endpoint_text":"- Translational parameter","definition_or_measurement_approach":"Translational endpoints mentioned but specific assays or measurements are not described in the provided record"}

Other endpoints

• {"endpoint_text":"- Progression free survival ratio (PFSr)","definition_or_measurement_approach":"Exploratory endpoint; definition/algorithm for PFSr not specified in the provided record"}

Germany

Earliest CTIS Part Ii Submission Date

23-09-2024

Latest Decision Or Authorization Date

18-12-2025

Processing Time Days

451

Number Of Sites

10

Number Of Participants

30

Primary sponsor

Full Name

Medical Center - University Of Freiburg

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"Bayer Vital GmbH","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"DKFZ (DKTK)","duties_or_roles":"Monetary support","organisation_type":""}