Treatment of Participants With Advanced and/or Refractory Solid Tumors (MK-5108-001)

NCT00543387 | Completed Phase 1 Results

• 3 other identifiers: 5108-0012007_598MK-5108-001
• Study Type: interventional
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will investigate the safety, side effects and how well the body tolerates MK-5108 as well as determine different doses of MK-5108 in participants with advanced and/or refractory solid tumors. The corresponding primary hypotheses of this study are that 1) administration of oral MK-5108 (twice daily for 2 out of 14-21 days) to participants with advanced and/or refractory solid tumors will be safe and tolerable, and that 2) the spectrum of side effects observed in these participants after administration of oral MK-5108 alone and in combination with docetaxel will be dose-dependent and allow for definition of a maximum tolerated dose (MTD).

Conditions

Cancer, Neoplasms, Tumors

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced an Adverse Event (AE)

  An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the Sponsor's product, was also an AE. The number of participants who experienced an AE was reported for each dose level group.

  From Day 1 of study treatment until 30 days following the last dose of study treatment (up to 577 days)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  DLTs were AEs considered related to study drug that prevented escalation of the drug dose. Hematologic DLTs included any Grade 5 hematologic toxicity, Grade 4 neutropenia lasting for ≥7 days in duration, Grade 3 or Grade 4 neutropenia with fever \>38.5°C and/or infection requiring antibiotic or anti-fungal treatment, and Grade 4 thrombocytopenia (≤25.0 x 10\^9/L). Non-hematologic DLT was defined as any Grade 3, 4, or 5 non-hematologic toxicity, with the specific exceptions of: Grade 3 nausea or Grade 3 vomiting, Grade 3 diarrhea, or Grade 3 dehydration occurring in the setting of inadequate compliance with supportive care and lasting for \<48 hours, alopecia, inadequately treated hypersensitivity reactions, or Grade 3 elevated transaminases of ≤1 week in duration. Any drug-related AE leading to a dose modification of MK-5108, or any unresolved drug-related toxicity persisting\>6 weeks, was also considered a DLT.

  Day 1 to Day 21 of study treatment (Cycle 1 for Panel 1, Panel 2, or Crossover)

Study Arms (11)

MK-5108 200 mg BID (Panel 1)

EXPERIMENTAL

Participants receive 200 mg of MK-5108 orally twice daily (BID) the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed).

Drug: MK-5108

MK-5108 400 mg BID (Panel 1)

EXPERIMENTAL

Participants receive 400 mg of MK-5108 orally BID the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed).

Drug: MK-5108

MK-5108 800 mg BID (Panel 1)

EXPERIMENTAL

Participants receive 800 mg of MK-5108 orally BID the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed).

Drug: MK-5108

MK-5108 1200 mg BID (Panel 1)

EXPERIMENTAL

Participants receive 1200 mg of MK-5108 orally BID the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed).

Drug: MK-5108

MK-5108 1500 mg BID (Panel 1)

EXPERIMENTAL

Participants receive 1500 mg of MK-5108 orally BID the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed).

Drug: MK-5108

MK-5108 1800 mg BID (Panel 1)

EXPERIMENTAL

Participants receive 1800 mg of MK-5108 orally BID the first 2 days of a 14-day cycle (cycle extended to 21 days if ≥Grade 2 toxicity observed).

Drug: MK-5108

MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Panel 2)

EXPERIMENTAL

Participants receive 100 mg of MK-5108 orally BID in combination with 60 mg/m\^2 Docetaxel administered intravenously (IV) the first 2 days of a 21-day cycle.

Drug: MK-5108; Drug: docetaxel

MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Panel 2)

EXPERIMENTAL

Participants receive 150 mg of MK-5108 orally BID in combination with 60 mg/m\^2 Docetaxel administered IV the first 2 days of a 21-day cycle.

Drug: MK-5108; Drug: docetaxel

MK-5108 225 mg BID + 60 mg/m^2 Docetaxel (Panel 2)

EXPERIMENTAL

Participants receive 150 mg of MK-5108 orally BID in combination with 60 mg/m\^2 Docetaxel administered IV the first 2 days of a 21-day cycle.

Drug: MK-5108; Drug: docetaxel

MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Crossover)

EXPERIMENTAL

After receiving treatment in Panel 1, one participant crossed over to Panel 2 per protocol following disease progression to receive 100 mg of MK-5108 orally BID in combination with 60 mg/m\^2 Docetaxel administered IV the first 2 days of a 21-day cycle.

Drug: MK-5108; Drug: docetaxel

MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Crossover)

EXPERIMENTAL

After receiving treatment in Panel 1, participants crossed over to Panel 2 per protocol following disease progression to receive 150 mg of MK-5108 orally BID in combination with 60 mg/m\^2 Docetaxel administered IV the first 2 days of a 21-day cycle.

Drug: MK-5108; Drug: docetaxel

Interventions

MK-5108 DRUG

MK-5108 will be administered orally, every 12 hours (Q12H) during the first 2 days of each cycle. Cycle length will be 14-21 days in Panel 1 and 21 days in Panel 2.

MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Crossover); MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Panel 2); MK-5108 1200 mg BID (Panel 1); MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Crossover); MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Panel 2); MK-5108 1500 mg BID (Panel 1); MK-5108 1800 mg BID (Panel 1); MK-5108 200 mg BID (Panel 1); MK-5108 225 mg BID + 60 mg/m^2 Docetaxel (Panel 2); MK-5108 400 mg BID (Panel 1); MK-5108 800 mg BID (Panel 1)

docetaxel DRUG

Docetaxel will be administered intravenously (I.V.) at a dose of 60 mg/m\^2 Q12H during the first 2 days of each 21-day cycle.

Also known as: Taxotere

MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Crossover); MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Panel 2); MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Crossover); MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Panel 2); MK-5108 225 mg BID + 60 mg/m^2 Docetaxel (Panel 2)

Eligibility Criteria

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

You may qualify if:

• \- Participant has a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy or progressed with standard therapy

You may not qualify if:

• Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks prior to study start or has not recovered from adverse events caused by therapy more than 4 weeks earlier
• Participant is currently participating or has participated in a study with an investigational compound or device within 4 weeks prior to signing informed consent
• Participant has received more than 2 courses of chemotherapy for metastatic disease
• Participant has had prolonged neutropenia or neutropenia with fever from previous chemotherapy treatment
• Participant has a primary central nervous system tumor
• Participant is a regular or recreational user of any illicit drugs or has a recent history within the last year of drug or alcohol abuse
• Participant is pregnant, breastfeeding or planning to have children during the study
• Participant is Human Immunodeficiency Virus (HIV) positive
• Participant has a history of Hepatitis B or C

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Amin M, Minton SE, LoRusso PM, Krishnamurthi SS, Pickett CA, Lunceford J, Hille D, Mauro D, Stein MN, Wang-Gillam A, Trull L, Lockhart AC. A phase I study of MK-5108, an oral aurora a kinase inhibitor, administered both as monotherapy and in combination with docetaxel, in patients with advanced or refractory solid tumors. Invest New Drugs. 2016 Feb;34(1):84-95. doi: 10.1007/s10637-015-0306-7. Epub 2015 Dec 1.

  PMID: 26620496 RESULT

MeSH Terms

Conditions

Neoplasms

Interventions

4-(3-chloro-2-fluorophenoxy)-1-((6-(1,3-thiazol-2-ylamino)pyridin to 2-yl)methyl) cyclohexanecarboxylic acid; Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: October 12, 2007
• First Posted: October 15, 2007
• Study Start: March 27, 2008
• Primary Completion: April 4, 2011
• Study Completion: April 4, 2011
• Last Updated: June 5, 2024
• Results First Posted: November 9, 2018

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share