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

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 1

Conditions: Tumor, Solid

Treatments: Drug: MK-8353

Study type: Interventional

Funder types: Industry

Identifiers

NCT01358331

P06203

2012-002696-33 (EudraCT Number)

MK-8353-001 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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25 participants in 6 patient groups

MK-8353 100 mg twice daily (BID)

Experimental group

Description:

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

Treatment:

Drug: MK-8353

MK-8353 200 mg BID

Experimental group

Description:

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

Treatment:

Drug: MK-8353

MK-6353 300 mg BID

Experimental group

Description:

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

Treatment:

Drug: MK-8353

MK-8353 350 mg BID

Experimental group

Description:

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

Treatment:

Drug: MK-8353

MK-8353 400 mg BID

Experimental group

Description:

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

Treatment:

Drug: MK-8353

MK-8353 800 mg BID

Experimental group

Description:

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

Treatment:

Drug: MK-8353