A multicentre, open label, Phase I trial of the MEK inhibitor MSC1936369B given orally to Subjects with Solid Tumours

Completed

• Conditions: Melanoma; skin cancer; 10040900

• Registration Number: NL-OMON36297
• Lead Sponsor: Merck

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 50

Inclusion Criteria

1. Pathologically-confirmed solid tumour which is locally advanced or metastatic, and either refractory after standard therapy for the disease or for which no effective standard therapy is available. In the regimen 3, regimen 2 food-effect, and BID cohorts, the tumour type will be restricted to melanoma.
2. Age 18 years or older.
3. Has read and understands the informed consent form and is willing and able to give informed consent. Fully understands requirements of the trial and willing to comply with all trial visits and assessments.
4. Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For the purposes of this trial, women of childbearing potential is defined as: *All female subjects after puberty unless they are post-menopausal for at least two years, are surgically sterile or are sexually inactive*.
5. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 2 weeks prior to, during and four weeks after the last dose trial medication. Adequate contraception is defined as follows: two barrier methods, or one barrier method with a spermicide or intrauterine device.

Exclusion Criteria

1. Bone marrow impairment as evidenced by Haemoglobin < 9.0 g/dL, Neutrophil count < 1.0 x 109/l, platelets < 100 x 109/l.
2. Renal impairment as evidenced by serum creatinine > 1.5 x ULN, and/or calculated creatinine clearance < 60 ml/min.
3. Liver function abnormality as defined by total bilirubin > 1.5 x ULN, or AST/ALT > 2.5 x ULN, for subjects with liver involvement AST/ALT > 5 x ULN.
4. INR > 1.5 x ULN
5. Serum calcium > 1 x ULN.
6. History of CNS metastases, unless subject has been previously treated for CNS metastases, is stable by CT scan without evidence of cerebral oedema, and has no requirements for corticosteroids or anticonvulsants.
7. History of difficulty swallowing, malabsorption or other chronic gastro-intestinal disease or conditions that may hamper compliance and/or absorption of the tested product.
8. Eastern Cooperative Oncology Group Performance status (ECOG PS) greater than 1.
9. Known HIV positivity, active hepatitis C, or active hepatitis B.
10. Has received chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anticancer therapy or surgical intervention within 28 Days or 5 half lives for non-cytotoxics (whichever is longer) of Day 1 of trial drug treatment (6 weeks for nitrosureas or mitomycin C).
11. Has received extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation.
12. Has received any investigational agent within 28 days or 5 half lives for non-cytotoxics (whichever is longer) of Day 1.
13. Has history of any other significant medical disease or intervention such as major gastric or small bowel surgery, recent drainage of significant volumes of ascites or pleural effusion or has a psychiatric condition that might impair the subject*s well being or preclude full participation in the trial.
14. Has significant cardiac conduction defects and/or pacemaker
15. Has hypertension uncontrolled by medication
16. Is a pregnant or nursing female.
17. Has retinal degenerative disease (Hereditary retinal degeneration or age-related macular degeneration), history of uveitis or history of retinal vein occlusion

Study & Design

• Study Type: Interventional
• Study Design: Not specified