Trial of MSC1936369B in Subjects With Solid Tumors

NCT00982865 | Completed Phase 1 Results

• 2 other identifiers: 280622007-004665-18
• Study Type: interventional
• Target: 182
• Locations: 4 countries
• Sites: 9

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

Keywords

MEK inhibitor; Cancer; Solid tumors

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) Over the First Cycle - Day 1 to 21

  DLT was defined as any of following toxicities at any dose level according to using National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) v3.0(CTCAE), probably or possibly related to trial medication by investigator or sponsor: a)Any Grade 3 or more non-haematological toxicity excluding: (i)Grade 3 asymptomatic increase in liver function tests (Aspartate Aminotransferase, Alanine transaminase, Alkaline Phosphatase reversible within 7 days for subjects without liver involvement, or grade 4 for subjects with liver involvement; (ii)Grade 3 vomiting if it is encountered despite adequate and optimal therapy (e.g. serotonin \[5HT3\] antagonists and corticosteroids); (iii)Grade 3 diarrhoea if it is encountered despite adequate and optimal anti diarrhoea therapy; b)Grade 4 neutropenia of \>5 days duration or febrile neutropenia lasting for more than 1 day; c)Grade 4 thrombocytopenia \>1 day or grade 3 with bleeding; d)Any treatment delay \>2 weeks due to drug-related AEs.

  Day 1 up to Day 21 of Cycle 1

Secondary Outcomes (45)

• Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation

  Baseline up to 253 weeks

• Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Leading to Death

  Baseline up to 253 weeks

• Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events

  Baseline up to 253 weeks

• Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours (h) post-dose on Cycle 1(C1) Day 1 (D1), Cycle 1 Day 12 (D12) and Cycle 3 (C3) Day 1

• Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect)

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1

Study Arms (4)

MSC1936369B Regimen 1

EXPERIMENTAL

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.

Drug: MSC1936369B

MSC1936369B Regimen 2

EXPERIMENTAL

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.

Drug: MSC1936369B

MSC1936369B Regimen 3 once daily

EXPERIMENTAL

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.

Drug: MSC1936369B

MSC1936369B Regimen 3 twice daily (BID)

EXPERIMENTAL

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.

Drug: MSC1936369B

Interventions

MSC1936369B DRUG

Also known as: Pimasertib

MSC1936369B Regimen 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Merck Serono S.A., Geneva: collaborator

Study Sites (9)

Westmead Hospital

Westmead, Australia

Location

Jules Bordet Institute

Brussels, B-1000, Belgium

Location

Ghent University Hospital

Ghent, Belgium

Location

Institute Bergonié

Bordeaux, France

Location

Hôpital Beaujon

Paris, 92118, France

Location

Hopital Saint Louis

Paris, France

Location

Centre Eugène Marquis

Rennes, France

Location

Institute Claudius Regaud

Toulouse, 03 31052, France

Location

Netherlands Cancer Institute - Antonie van Leeuwenhoek Hospital

Amsterdam, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 33211315 DERIVED

• 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.

  PMID: 33170484 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2009
• First Posted: September 23, 2009
• Study Start: December 31, 2007
• Primary Completion: March 31, 2013
• Study Completion: April 30, 2016
• Last Updated: October 23, 2018
• Results First Posted: October 23, 2018

Record last verified: 2018-02

Locations

NL (1); BE (2); FR (5); AU (1)