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

NCT01358331 | Terminated Phase 1 Results

• 3 other identifiers: P062032012-002696-33MK-8353-001
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-Limiting Toxicities (DLTs)

  DLT was derived from the toxicities observed during the first cycle (28 days) for each dose level. DLT is defined as any hematologic or non-hematologic toxicity ≥Grade 3 as pre-specified per protocol, or drug-related toxicity, regardless of Common Terminology Criteria for Adverse Events (CTCAE) grade that causes \>20% of the intended total number of doses in Cycle 1 to be missed.

  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

• Number of Participants With Overall Response Rate

  Overall Response rate is defined as the number of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  Baseline, and every 8 weeks until disease progression or discontinuation from study up to approximately 10 months

Study Arms (6)

MK-8353 100 mg twice daily (BID)

EXPERIMENTAL

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

Drug: MK-8353

MK-8353 200 mg BID

EXPERIMENTAL

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

Drug: MK-8353

MK-6353 300 mg BID

EXPERIMENTAL

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

Drug: MK-8353

MK-8353 350 mg BID

EXPERIMENTAL

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

Drug: MK-8353

MK-8353 400 mg BID

EXPERIMENTAL

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

Drug: MK-8353

MK-8353 800 mg BID

EXPERIMENTAL

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

Drug: MK-8353

Interventions

MK-8353 DRUG

Administered orally twice daily for 28 days for each cycle

MK-6353 300 mg BID; MK-8353 100 mg twice daily (BID); MK-8353 200 mg BID; MK-8353 350 mg BID; MK-8353 400 mg BID; MK-8353 800 mg BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 29467321 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

MK-8353

Limitations and Caveats

The study was terminated early due to business reasons.

Results Point of Contact

• Title: Clinical Trials Disclosure
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Study Officials

• Medical Director

  Merck Sharpe & Dohme Corp.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2011
• First Posted: May 23, 2011
• Study Start: November 4, 2011
• Primary Completion: May 20, 2014
• Study Completion: May 20, 2014
• Last Updated: April 2, 2020
• Results First Posted: April 2, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share