Clinical trial NCT01358331: A Study of the Safety, Tolerability, and Efficacy of MK-8353 in Participants With Advanced Solid Tumors (MK-8353-001)
Official title: A Phase 1 Study to Evaluate the Safety, Tolerability and Efficacy of MK-8353 (Formerly SCH 900353) in Subjects With Advanced Solid Tumors (Protocol No. 001 (Formerly P06203))
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Tumor, Solid
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-05-23
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study of the safety, tolerability, and efficacy of MK-8353 (formerly SCH 900353) given as single agent oral therapy for participants with advanced solid tumors will be done into two parts. In Part 1a, there will be a dose escalation to find the preliminary maximum tolerated dose (MTD), and in Part 1b, dose confirmation to find out the recommended Phase 2 dose (RPTD) that will be used in Part 2 of the study. In Part 2 of the study, participants with certain types of metastatic melanoma or metastatic colorectal cancer will be treated to see if MK-8353 is effective as single agent therapy.


Eligibility criteria: Inclusion Criteria:

* Pathologically/histologically confirmed solid tumor (metastatic or locally advanced disease) that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist.
* Participants of childbearing potential must have negative pregnancy test; females and males must agree to use effective contraception during the course of the trial and for 90 days after stopping study drug.
* For Part 1b and Part 2, participant with metastatic melanoma or metastatic colorectal cancer with at least one measurable lesion
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with a life expectancy of ≥3 months.
* Adequate organ function.

Exclusion Criteria:

* Unstable or progressing central nervous system (CNS) metastasis unless asymptomatic for 3 months, with no need for steroids or antiseizure medications.
* Active gastrointestinal disease or a disorder or a history of surgery that significantly alters gastrointestinal motility or absorption.
* Has not recovered from previous therapy and had any chemotherapy, biologic, or hormonal therapy within 4 weeks of study enrollment.
* Radiation therapy (except palliative radiation to bone lesions) within 4 weeks of study enrollment.
* More than 3 prior regimens of chemotherapy, biologic therapy, hormonal therapy, or investigational drugs not including adjuvant or neoadjuvant treatments.
* Clinically relevant cardiovascular, hepatic, neurologic, endocrine, or other major systemic diseases.
* Mean QTcF interval (interval on the electrocardiogram corrected for heart rate using Fridericia's correction) \> 450 msec at baseline.
* Known Human Immunodeficiency Virus (HIV) infection, hepatitis infection, or tuberculosis infection.
* Current participation in any other interventional clinical study.
* History of significant eye disease, including glaucoma, retinopathy, or retinal vein occlusion.

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Cycles of 28 days, up to approximately 9 months treatment and a 30-day follow-up period for a total time of up to approximately 10 months
measure: Number of Participants With Overall Response Rate
timeFrame: Baseline, and every 8 weeks until disease progression or discontinuation from study up to approximately 10 months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharpe & Dohme Corp.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Moschos SJ, Sullivan RJ, Hwu WJ, Ramanathan RK, Adjei AA, Fong PC, Shapira-Frommer R, Tawbi HA, Rubino J, Rush TS 3rd, Zhang D, Miselis NR, Samatar AA, Chun P, Rubin EH, Schiller J, Long BJ, Dayananth P, Carr D, Kirschmeier P, Bishop WR, Deng Y, Cooper A, Shipps GW, Moreno BH, Robert L, Ribas A, Flaherty KT. Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with advanced solid tumors. JCI Insight. 2018 Feb 22;3(4):e92352. doi: 10.1172/jci.insight.92352. eCollection 2018 Feb 22.