A Phase I Study of Oral MEK162 in Japanese Patients With Advanced Solid Tumors

In this study, MEK162 will be administered to Japanese patients with advanced solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists. The trial will investigate the safety and tolerability and determine the MTD of MEK162 in Japanese patients.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: MEK162

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya-city, Aichi, Japan, 466-8560
      • Pfizer Investigative Site
  • Oita
    • Yufu, Oita, Japan, 879-5593
      • Pfizer Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with histologically-confirmed, advanced unresectable solid tumors who have progressed within three months before screening/baseline visit.
• Availability of a representative formalin fixed paraffin embedded tumor tissue sample.
• At least one measurable or non-measurable lesion
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Good organ (hepatic, kidney, BM) function at screening/baseline visit.

Exclusion Criteria:

• Brain metastasis unless treated and free of signs/symptoms attributable to brain metastasis in the absence of corticosteroid therapy and anti-epileptic therapy.
• Impaired cardiac function or clinically significant cardiac disease incl. unstable angina pectoris ≤ 3 months prior to starting study drug and Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug.
• Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: MEK162; MEK162 will be administered orally once on Day 1 of Cycle 1 and continuously on a BID schedule, starting on Day 2 of Cycle 1 and on Day 1 of subsequent cycles. Each cycle will be 28 days in duration. Dose will be escalated and starting dose is 30 mg. Any doses that are missed should be skipped and should not be replaced or made up during the evening dosing or on a subsequent day, whichever applies. The prescribed BID doses should be taken 12 ± 2 hrs apart.

Drug: MEK162; MEK162 in an oral formulation. It is a film-coated capsule-shape tablets (i.e. caplets).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose limiting toxicities	Incidence of frequency of Dose limiting toxicities during first 4 weeks will be measured according to the commen terminology criteria for adverse events (CTCAE).	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events and serious adverse events, changes in laboratory values	Incidence and severity of adverse events and serious adverse events, changes in laboratory values will be measured during the treatment.	4 months
Plasma concentration of MEK162 and AR00426032active metabolite of MEK162 and derived PK parameters of MEK162 and the active metabolite.	Plasma concentration of MEK162 and active metabolite of MEK162 and derived PK parameters of MEK162 and the active metabolite will be measured with serial plasma samples during treatment for first 2 months.	2 months
Tumor responses according to RECIST 1.1	Tumor responses will be measured according to RECIST 1.1	4 months
Levels of p-ERK in tumor and skin	Levels of p-ERK in tumor during treatment and skin for first 2 weeks will be measured.	4 months

Collaborators and Investigators

• Sponsor: Array Biopharma, now a wholly owned subsidiary of Pfizer

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): April 1, 2014
• Study Completion (ACTUAL): February 1, 2018

Study Registration Dates

• First Submitted: November 8, 2011
• First Submitted That Met QC Criteria: November 9, 2011
• First Posted (ESTIMATE): November 10, 2011

Study Record Updates

• Last Update Posted (ACTUAL): October 5, 2020
• Last Update Submitted That Met QC Criteria: September 30, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: MEK, Advanced solid tumor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CMEK162X1101