Trial of MSC1936369B in Subjects With Solid Tumors

NCT ID: NCT00982865

Last Updated: 2018-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 182 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2016-04-30

Brief Summary

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.

Conditions

Solid Tumors; Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MSC1936369B Regimen 1

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.

Group Type: EXPERIMENTAL

MSC1936369B

Intervention Type: DRUG

MSC1936369B Regimen 2

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.

Group Type: EXPERIMENTAL

MSC1936369B

Intervention Type: DRUG

MSC1936369B Regimen 3 once daily

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.

Group Type: EXPERIMENTAL

MSC1936369B

Intervention Type: DRUG

MSC1936369B Regimen 3 twice daily (BID)

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.

Group Type: EXPERIMENTAL

MSC1936369B

Intervention Type: DRUG

Interventions

MSC1936369B

Intervention Type: DRUG

MSC1936369B

Intervention Type: DRUG

MSC1936369B

Intervention Type: DRUG

MSC1936369B

Intervention Type: DRUG

Other Intervention Names

Pimasertib; Pimasertib; Pimasertib; Pimasertib

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Serono S.A., Geneva

INDUSTRY

Sponsor Role: collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Westmead Hospital

Westmead, , Australia

Jules Bordet Institute

Brussels, , Belgium

Ghent University Hospital

Ghent, , Belgium

Institute Bergonié

Bordeaux, , France

Hôpital Beaujon

Paris, , France

Hopital Saint Louis

Paris, , France

Centre Eugène Marquis

Rennes, , France

Institute Claudius Regaud

Toulouse, , France

Netherlands Cancer Institute - Antonie van Leeuwenhoek Hospital

Amsterdam, , Netherlands

Countries

Australia; Belgium; France; Netherlands

References

Lebbe C, Italiano A, Houede N, Awada A, Aftimos P, Lesimple T, Dinulescu M, Schellens JHM, Leijen S, Rottey S, Kruse V, Kefford R, Raymond E, Faivre S, Pages C, Gomez-Roca C, Schueler A, Goodstal S, Massimini G, Delord JP. Selective Oral MEK1/2 Inhibitor Pimasertib in Metastatic Melanoma: Antitumor Activity in a Phase I, Dose-Escalation Trial. Target Oncol. 2021 Jan;16(1):47-57. doi: 10.1007/s11523-020-00767-1.

Reference Type: DERIVED

PMID: 33211315 (View on PubMed)

Delord JP, Italiano A, Awada A, Aftimos P, Houede N, Lebbe C, Pages C, Lesimple T, Dinulescu M, Schellens JHM, Leijen S, Rottey S, Kruse V, Kefford R, Faivre S, Gomez-Roca C, Scheuler A, Massimini G, Raymond E. Selective Oral MEK1/2 Inhibitor Pimasertib: A Phase I Trial in Patients with Advanced Solid Tumors. Target Oncol. 2021 Jan;16(1):37-46. doi: 10.1007/s11523-020-00768-0.

Reference Type: DERIVED

PMID: 33170484 (View on PubMed)

Other Identifiers

2007-004665-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

28062

Identifier Type: -

Identifier Source: org_study_id