Tumor, SolidPhase 1NCT01358331

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

A Phase 1 study testing MK-8353 in people with Tumor, Solid, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Tumor, Solid
What is being tested?: MK-8353
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: No sites listed yet
Study dates: 4 Nov 2011to 20 May 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 10Show fewer

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.

About this study

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))

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
Being tested: MK-8353
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-8353Drug
Administered orally twice daily for 28 days for each cycle

Study groups in NCT01358331
Study group	Role	What they receive
MK-8353 100 mg twice daily (BID)	Experimental	100 mg capsules administered orally twice daily for 28 days for each cycle Receives: Drug: MK-8353
MK-8353 200 mg BID	Experimental	200 mg capsules administered orally twice daily for 28 days for each cycle Receives: Drug: MK-8353
MK-6353 300 mg BID	Experimental	300 mg capsules administered orally twice daily for 28 days for each cycle Receives: Drug: MK-8353
MK-8353 350 mg BID	Experimental	350 mg capsules administered orally twice daily for 28 days for each cycle Receives: Drug: MK-8353
MK-8353 400 mg BID	Experimental	400 mg capsules administered orally twice daily for 28 days for each cycle Receives: Drug: MK-8353
MK-8353 800 mg BID	Experimental	800 mg capsules administered orally twice daily for 28 days for each cycle Receives: Drug: MK-8353

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Nov 201120 May 2014

First posted23 May 2011 (estimated)
Study start4 Nov 2011
Primary completion20 May 2014
Study completion20 May 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Tumor, SolidStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01358331
Sponsor's protocol ID: P06203
Other IDs: 2012-002696-33, MK-8353-001
Status last verified: Mar 2020
First submitted: 19 May 2011
Last updated: 2 Apr 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

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.
PubMed 29467321

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

All Tumor, Solid trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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))
ClinicalTrials.gov ID: NCT01358331
Acronym / sponsor ID: P06203
Conditions: Tumor, Solid
Phase: Phase 1
Study type: Interventional
Recruitment status: Terminated
Enrolment: 25 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 4 Nov 2011 (actual)
Primary completion: 20 May 2014 (actual)
Study completion: 20 May 2014 (actual)
First posted: 23 May 2011 (estimated)
Results: Posted 2 Apr 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
MK-8353 100 mg twice daily (BID)	Experimental	Drug: MK-8353100 mg capsules administered orally twice daily for 28 days for each cycle
MK-8353 200 mg BID	Experimental	Drug: MK-8353200 mg capsules administered orally twice daily for 28 days for each cycle
MK-6353 300 mg BID	Experimental	Drug: MK-8353300 mg capsules administered orally twice daily for 28 days for each cycle
MK-8353 350 mg BID	Experimental	Drug: MK-8353350 mg capsules administered orally twice daily for 28 days for each cycle
MK-8353 400 mg BID	Experimental	Drug: MK-8353400 mg capsules administered orally twice daily for 28 days for each cycle
MK-8353 800 mg BID	Experimental	Drug: MK-8353800 mg capsules administered orally twice daily for 28 days for each cycle

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (10 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MK-8353Administered orally twice daily for 28 days for each cycle	Drug	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

Primary outcome

Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: 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
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.
Number of Participants With Overall Response Rate
Time frame: Baseline, and every 8 weeks until disease progression or discontinuation from study up to approximately 10 months
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.

Results and safety

Results posted to the registry on 2 Apr 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MK-8353 100 mg Twice Daily (BID)	2	0
MK-8353 200 mg BID	3	0
MK-8353 300 mg BID	4	0
MK-8353 350 mg BID	3	0
MK-8353 400 mg BID	7	0
MK-8353 800 mg BID	6	0

Primary outcome: Number of Participants With Dose-Limiting Toxicities (DLTs)

Time frame: 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. Unit: Participants

Measure	MK-8353 400 mg BID n = 6	MK-8353 800 mg BID n = 2
Grade 3 Maculopapular Rash	1	0
Grade 3 Diarrhea	1	0
Grade 3 fatigue	0	1
Grade 3 nausea/vomiting/diarrhea	0	1
Grade 4	0	0
Grade 5	0	0

Population analysed: Analysis population includes all participants who received at least one dose of MK-8353 and completed Cycle 1 of Part 1 or discontinued due to toxicity. Participants who discontinued treatment due to reasons other than toxicity were not included.

Primary outcome: Number of Participants With Overall Response Rate

Time frame: Baseline, and every 8 weeks until disease progression or discontinuation from study up to approximately 10 months. Number. Unit: Participants

Measure	MK-8353 300 mg BID n = 4	MK-8353 350 mg BID n = 3	MK-8353 400 mg BID n = 6
Partial Response	1	1	0
Partial Response Unconfirmed	0	0	1
Complete Response	0	0	0

Population analysed: The analysis population is defined as all participants who received at least 1 dose of MK-8353 and had at least 1 post-baseline efficacy assessment. Participants who received at least one dose but had no post-baseline assessment were counted as "not evaluable" and were not included in this analysis.

Adverse events

Time frame: 28-days per cycle up to 9 months plus a 30-day follow-up period for a total of approximately up to 10 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MK-8353 100 mg Twice Daily (BID)	1 of 2 (50%)	2 of 2 (100%)	0 of 2
MK-8353 200 mg BID	1 of 3 (33.3%)	3 of 3 (100%)	1 of 3
MK-8353 300 mg BID	1 of 4 (25%)	4 of 4 (100%)	1 of 4
MK-8353 350 mg BID	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
MK-8353 400 mg BID	3 of 7 (42.9%)	7 of 7 (100%)	1 of 7
MK-8353 800 mg BID	5 of 6 (83.3%)	6 of 6 (100%)	2 of 6

Limitations and caveats (from the sponsor): The study was terminated early due to business reasons.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29467321Moschos 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.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Related trials for Tumor, Solid

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharpe & Dohme Corp.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-8353 in people with Tumor, Solid, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01358331, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2020; AzTrials last refreshed its copy on 8 Nov 2026.