Trial of MSC1936369B in Subjects With Solid Tumors

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 1

Conditions: Cancer; Solid Tumors

Treatments: Drug: MSC1936369B

Study type: Interventional

Funder types: Industry

Identifiers

NCT00982865

2007-004665-18 (EudraCT Number)

28062

Details and patient eligibility

About

This is a first in man trial with a primary objective being the determination of the Maximum Tolerated dose (MTD) and the dose-limiting toxicity (DLT) in several regimens of MEK inhibitor MSC1936369B administered orally once a day, in subjects with malignant solid tumors to see how safe is treatment with MSC1936369B.

Enrollment: 182 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Pathologically-confirmed solid tumor 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 tumor type will be restricted to melanoma.
• Age greater than or equal to (>=) 18 years
• 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

Exclusion criteria

• Bone marrow impairment as evidenced by Haemoglobin less than (<) 9.0 gram per deciliter (g/dL), Neutrophil count < 1.0*10^9/Liter, platelets < 100*10^9/Liter
• Renal impairment as evidenced by serum creatinine > 1.5*upper limit normal (ULN), and/or calculated creatinine clearance < 60 milliliter per minute (mL/min)
• Liver function abnormality as defined by total bilirubin > 1.5*ULN, or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5*ULN, for subjects with liver involvement AST/ALT > 5*ULN
• INR > 1.5*ULN
• Serum calcium > 1*ULN
• History of central nervous system (CNS) metastases, unless subject has been previously treated for CNS metastases, is stable by computer tomography (CT) scan without evidence of cerebral oedema, and has no requirements for corticosteroids or anticonvulsants
• History of difficulty swallowing, malabsorption or other chronic gastro-intestinal disease or conditions that may hamper compliance and/or absorption of the tested product
• Eastern Cooperative Oncology Group Performance status (ECOG PS) greater than (>) 1
• Known human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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182 participants in 4 patient groups

MSC1936369B Regimen 1

Experimental group

Description:

Subjects will be administered MSC1936369B (pimasertib) capsules 1 to 120 milligram (mg) orally, once daily (QD) on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until progressive disease (PD) or intolerable toxicity or investigator/subject decision.

Treatment:

Drug: MSC1936369B

Drug: MSC1936369B

Drug: MSC1936369B

Drug: MSC1936369B

MSC1936369B Regimen 2

Experimental group

Description:

MSC1936369B Regimen 2 (Without Food Effect): Subjects will be administered MSC1936369B capsules 1 to 255 mg orally QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (With Food Effect): : Subjects will be administered MSC1936369B capsules 90 or 150 mg orally QD on Day 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects in the Regimen 2 FE cohort were assigned in a 1:1 ratio to either the fed/fasted sequence or fasted/fed sequence for Day 1 of Cycle 1 and Day 1 of Cycle 2.

Treatment:

Drug: MSC1936369B

Drug: MSC1936369B

Drug: MSC1936369B

Drug: MSC1936369B

MSC1936369B Regimen 3 once daily

Experimental group

Description:

Subjects will be administered MSC1936369B capsules 60 to 90 mg orally QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.

Treatment:

Drug: MSC1936369B

Drug: MSC1936369B

Drug: MSC1936369B

Drug: MSC1936369B

MSC1936369B Regimen 3 twice daily (BID)

Experimental group

Description:

Subjects will be administered MSC1936369B capsules 45 to 75 mg orally BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.

Treatment:

Drug: MSC1936369B

Drug: MSC1936369B

Drug: MSC1936369B

Drug: MSC1936369B