Overview

This trial is active, not recruiting.

Conditions solid tumors, cancer
Treatments msc1936369b
Phase phase 1
Sponsor Merck KGaA
Collaborator Merck Serono S.A., Geneva
Start date December 2007
End date March 2013
Trial size 205 participants
Trial identifier NCT00982865, 2007-004665-18, 28062

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Orally once daily on Days 1 to 5, 8 to 12 and 15 to 19 of a 21-day cycle.
msc1936369b MEK Inhibitor
MSC1936369B at escalating dose levels. Number of cycles: until progression or unacceptable toxicity develops
(Experimental)
Orally once a day on Days 1 to 15 of a 21-day cycle.
msc1936369b MEK Inhibitor
MSC1936369B at escalating doses levels. Number of cycles: until progression or unacceptable toxicity develops
(Experimental)
Orally once a day from Day 1 to 21.
msc1936369b MEK Inhibitor
MSC1936369B at escalating doses levels. Number of cycles: until progression or unacceptable toxicity develops
(Experimental)
Orally twice a day from either Days 1 to 15 of a 21-day cycle (similar to Regimen 2) or up to Day 21 (similar to Regimen 3).
msc1936369b MEK Inhibitor
MSC1936369B at escalating doses levels. Number of cycles: until progression or unacceptable toxicity develops

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
The number and proportion of subjects experiencing treatment-emergent adverse events (TEAE).
time frame: Until end of treatment / study
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
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
Values and changes over time in PD markers in circulating PBMC, circulating tumor 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
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 tumor evaluations assessed at the end of each 2 cycles.
time frame: Until end of treatment / study

Eligibility Criteria

Male or female participants at least 18 years old.

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 ≥ 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.

Additional Information

Official title A Multicenter, Open Label, Phase I Trial of the MEK Inhibitor MSC1936369B Given Orally to Subjects With Solid Tumours
Trial information was received from ClinicalTrials.gov and was last updated in October 2015.
Information provided to ClinicalTrials.gov by Merck KGaA.