A Study of the Safety, Tolerability, and Efficacy of MK-8353 in Participants With Advanced Solid Tumors (MK-8353-001)

NCT ID: NCT01358331

Last Updated: 2020-04-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-04
• Study Completion Date: 2014-05-20

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.

Conditions

Tumor, Solid

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MK-8353 100 mg twice daily (BID)

100 mg capsules administered orally twice daily for 28 days for each cycle

Group Type: EXPERIMENTAL

MK-8353

Intervention Type: DRUG

Administered orally twice daily for 28 days for each cycle

MK-8353 200 mg BID

200 mg capsules administered orally twice daily for 28 days for each cycle

Group Type: EXPERIMENTAL

MK-8353

Intervention Type: DRUG

Administered orally twice daily for 28 days for each cycle

MK-6353 300 mg BID

300 mg capsules administered orally twice daily for 28 days for each cycle

Group Type: EXPERIMENTAL

MK-8353

Intervention Type: DRUG

Administered orally twice daily for 28 days for each cycle

MK-8353 350 mg BID

350 mg capsules administered orally twice daily for 28 days for each cycle

Group Type: EXPERIMENTAL

MK-8353

Intervention Type: DRUG

Administered orally twice daily for 28 days for each cycle

MK-8353 400 mg BID

400 mg capsules administered orally twice daily for 28 days for each cycle

Group Type: EXPERIMENTAL

MK-8353

Intervention Type: DRUG

Administered orally twice daily for 28 days for each cycle

MK-8353 800 mg BID

800 mg capsules administered orally twice daily for 28 days for each cycle

Group Type: EXPERIMENTAL

MK-8353

Intervention Type: DRUG

Administered orally twice daily for 28 days for each cycle

Interventions

MK-8353

Administered orally twice daily for 28 days for each cycle

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharpe & Dohme Corp.

References

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.

Reference Type: DERIVED

PMID: 29467321 (View on PubMed)

Other Identifiers

2012-002696-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-8353-001

Identifier Type: OTHER

Identifier Source: secondary_id

P06203

Identifier Type: -

Identifier Source: org_study_id