A Multicentre, Open Label, Phase I Trial in Japan of the MEK Inhibitor Pimasertib Given Orally to Subjects With Solid Tumors as Monotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Merck KGaA
Sponsor:
Collaborator:
Merck Serono Co., Ltd., Japan
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01668017
First received: August 15, 2012
Last updated: September 4, 2012
Last verified: September 2012
  Purpose

This is a two-part trial. "Solid tumor" in this protocol means solid tumor excluding hepatocellular carcinoma (HCC).

Part 1: Dose Escalation Phase in subjects with solid tumor (Cohort A) and HCC (Cohort B). The dose will be increased from 45 mg twice a day (BID) with 3+3 cohort method up to the recommended phase 2 dose (RP2D) of pimasertib established as single agent in the global studies for each arm independently.

Part 2: The Maximum Tolerated Dose (MTD) defined in Part 1 will be confirmed in more subjects in Cohort A (N=18) and Cohort B (N=6) separately.


Condition Intervention Phase
Advanced Solid Tumors
Hepatocellular Carcinoma
Drug: Pimasertib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicentre, Open Label, Phase I Trial in Japan of the MEK Inhibitor Pimasertib Given Orally to Subjects With Solid Tumors as Monotherapy

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of Participants Who Experienced at least one Dose Limiting Toxicity (DLT) During Treatment Cycle 1 (days 1-21) by arm and treatment level [ Time Frame: Days 1-21 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants who experienced treatment-emergent adverse events (TEAEs) [ Time Frame: Day 1 up to approximately Day 84 (end of cycle 4) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters [ Time Frame: Day 1 up to approximately Day 84 (end of cycle 4) ] [ Designated as safety issue: No ]
    Maximum concentration (Cmax), time to maximum concentration (tmax), area under the curve from hours 0-24 (AUC0-24), area under the curve over time (AUCt), apparent terminal half-life (t1/2), apparent clearance (CL/f), apparent clearance at steady-state (CLss/f), apparent volume of distribution at terminal phase (Vz/f), apparent volume of distribution at steady-state (Vss/f), accumulation ratio for AUC (Racc(AUC)), accumulation ratio for Cmax (Racc(Cmax))

  • Participants best overall response as Assessed by the Investigator [ Time Frame: Day 1 up to approximately Day 84 (end of cycle 4) ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: August 2012
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pimasertib
Pimasertib taken as assigned in doses between the 45 mg twice a day (BID) up to the recommended phase 2 dose (RP2D) expected to be between 60-75mg BID.
Drug: Pimasertib
Pimasertib will be supplied as 15 and 30 mg hard gelatin capsules. Pimasertib will be taken orally twice a day continuously. Treatment will be administered in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.

  Eligibility

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

Inclusion Criteria:

Cohort A: A histologically or cytologically confirmed diagnosis of advanced solid tumors which is either refractory after standard therapy for the disease or for which no effective standard therapy is available. Archived tumor tissue available or biopsy of tumor tissue needs to be performed.

Cohort B: A histologically or cytologically confirmed diagnosis of advanced hepatocellular carcinoma (HCC) which is either refractory after standard therapy for the disease or for which no effective standard therapy is available. Archived tumor tissue available or biopsy of tumor tissue needs to be performed. Subjects with Child Pugh A.

  • Male or female Japanese, age ≥ 18 years.
  • Subject has read and understands the informed consent form and is willing and able to give informed consent. The subject fully understands requirements of the trial and is willing to comply with all trial visits and assessments.
  • Women of childbearing potential must have a negative blood pregnancy test at the screening visit.
  • Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 2 weeks prior to, during and four weeks after the last dose investigational medicinal product (IMP).
  • Life expectancy of at least 3 months

Exclusion Criteria:

Hematological abnormality Cohort A: Hematological test abnormalities of Hemoglobin < 9.0 g/dL, Neutrophil count < 1.0*10^9/L and Platelet count < 100*10^9/L.

Cohort B: Hematological test abnormalities of Hemoglobin < 9.0 g/dL, Neutrophil count < 1.0*10^9/L, Platelet count < 75*10^9/L, subjects with hepatic encephalopathy

  • Renal impairment as evidenced by serum creatinine > 1.5*upper limit of normal (ULN), and calculated creatinine clearance < 60 mL/min by Cockcroft-Gault formula.
  • Liver function abnormality of Total Bilirubin > 1.5*ULN, or aspartate transaminase 9AST) or alkaline phosphatase (ALT)> 2.5*ULN. For subjects with HCC or liver involvement AST/ALT > 5*ULN.
  • History of central nervous system (CNS) metastases, unless subject has been previously treated for CNS metastases
  • History of difficulty swallowing, malabsorption or other chronic gastro-intestinal disease or conditions
  • Eastern Cooperative Oncology Group Performance status (ECOG PS) greater than 1.
  • Has received chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anticancer therapy (including any investigational agent) or surgical intervention within 28 days or 5 half lives for non-cytotoxics of registration.
  • Baseline corrected QT interval on screening ECG (QTc) ≥ 480 ms or left ventricular ejection fraction (LVEF) < 40% on screening echocardiogram
  • Cohort B: Subjects with hepatic encephalopathy, remarkable ascites and subjects with history of esophageal varices rupture within 6 months (subjects with symptom improvement after treatment are eligible)
  • Other serious illness or medical conditions.
  • Retinal degenerative disease.
  • Previous treatment with MEK inhibitors.
  • Legal incapacity or limited legal capacity.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01668017

Contacts
Contact: Yukito Kuwahara, Clinical Trial Leader yukito.kuwahara@merckgroup.com

Locations
Japan
Please contact Recruiting
Merck Serono Co., Ltd for recruiting locations in, Japan
Contact    81-3-6853-8630      
Sponsors and Collaborators
Merck KGaA
Merck Serono Co., Ltd., Japan
Investigators
Principal Investigator: Department of GI Oncology/Gastroenterology National Cancer Centre Hospital East
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01668017     History of Changes
Other Study ID Numbers: EMR 200066-010
Study First Received: August 15, 2012
Last Updated: September 4, 2012
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Merck KGaA:
Advanced solid tumors
Hepatocellular carcinoma
cancer, liver

Additional relevant MeSH terms:
Carcinoma
Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on August 28, 2014