Trial of MSC1936369B in Subjects With Solid Tumours - Full Text View

Purpose

This is a first in men 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 tumours to see how safe is treatment with MSC1936369B.

Condition	Intervention	Phase
Solid Tumors Cancer	Drug: MSC1936369B	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Multicenter, Open Label, Phase I Trial of the MEK Inhibitor MSC1936369B Given Orally to Subjects With Solid Tumours

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Merck KGaA:

Primary Outcome Measures:

The number and proportion of subjects experiencing at least a Dose-Limiting Toxicity (DLT) over the first cycle - day 1 to 21 for each regimen separately. [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The number and proportion of subjects experiencing treatment-emergent adverse events (TEAE). [ Time Frame: Until end of treatment / study ] [ Designated as safety issue: No ]
The number and proportion of subjects experiencing clinically significant changes in a laboratory parameter and/or vital signs judged to be related to the trial medication. [ Time Frame: Until end of treatment / study ] [ Designated as safety issue: No ]
Plasma and urine PK parameters of MSC1936369B Plasma and urine PK parameters of MSC1936369B and effect of food on PK at MTD or lower dose. [ Time Frame: Until end of treatment / study ] [ Designated as safety issue: No ]
Values and changes over time in PD markers in circulating PBMC, circulating tumour cells, apoptosis markers, blood circulating markers and in some subjects in tissue samples: apoptosis, phospho-ERK, marker of proliferation. [ Time Frame: Until end of treatment / study ] [ Designated as safety issue: No ]
Number and proportion of subjects with clinical benefit (Complete Response, Partial Response or stable disease) and progressive disease based on the best overall response which depends on the tumour evaluations assessed at the end of each 2 cycles. [ Time Frame: Until end of treatment / study ] [ Designated as safety issue: No ]

Estimated Enrollment:	162
Study Start Date:	January 2008
Estimated Study Completion Date:	February 2013
Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: MSC1936369B Regimen 1 Orally once daily on days 1 to 5, 8 to 12 and 15 to 19 of a 21 day cycle	Drug: MSC1936369B MSC1936369B at escalating dose levels. Number of cycles: until progression or unacceptable toxicity develops Other Names: MEK Inhibitor Pimasertib
Experimental: MSC1936369B Regimen 2 Orally once a day on days 1 to 15 of a 21 day cycle	Drug: MSC1936369B MSC1936369B at escalating doses levels. Number of cycles: until progression or unacceptable toxicity develops Other Names: MEK Inhibitor Pimasertib
Experimental: MSC1936369B Regimen 3 Orally once a day from day 1 to day 21	Drug: MSC1936369B MSC1936369B at escalating doses levels. Number of cycles: until progression or unacceptable toxicity develops Other Names: MEK Inhibitor Pimasertib
Experimental: MSC1936369B Regimen 3 BID Orally twice a day from day 1 to day 21	Drug: MSC1936369B MSC1936369B at escalating doses levels. Number of cycles: until progression or unacceptable toxicity develops Other Names: MEK Inhibitor Pimasertib

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.
Age ≥ 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 < 9.0 g/dL, Neutrophil count < 1.0 x 109/l, platelets < 100 x 109/l.
Renal impairment as evidenced by serum creatinine > 1.5 x ULN, and/or calculated creatinine clearance < 60 ml/min.
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.
INR > 1.5 x ULN.
Serum calcium > 1 x ULN.
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.
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 HIV positivity, active hepatitis C, or active hepatitis B.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00982865

Locations

Australia
Westmead Hospital
Westmead, Australia
Belgium
Jules Bordet Institute
Brussels, Belgium, B-1000
Ghent University Hospital
Ghent, Belgium
France
Institute Bergonié
Bordeaux, France
Hopital Saint Louis
Paris, France
Hôpital Beaujon
Paris, France, 92118
Centre Eugène Marquis
Rennes, France
Institute Claudius Regaud
Toulouse, France, 03 31052
Netherlands
Netherlands Cancer Institute - Antonie van Leeuwenhoek Hospital
Amsterdam, Netherlands

Sponsors and Collaborators

Merck KGaA

Merck Serono S.A., Geneva

Investigators

Study Director:

Narmyn Rejeb, MD

Merck Serono S.A., Geneva

More Information

No publications provided

Responsible Party:	Merck KGaA
ClinicalTrials.gov Identifier:	NCT00982865 History of Changes
Other Study ID Numbers:	28062
Study First Received:	September 22, 2009
Last Updated:	December 5, 2012
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Belgium: Ministry of Social Affairs, Public Health and the Environment Australia: Therapeutic Good Administration Netherlands: Central Committee on Research Involving Human Subjects

Keywords provided by Merck KGaA:

MEK inhibitor
Cancer
Solid tumours

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on May 21, 2013