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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Cancer, Neoplasms, Tumors

Treatments: Drug: docetaxel; Drug: MK-5108

Study type: Interventional

Funder types: Industry

Identifiers

NCT00543387

MK-5108-001 (Other Identifier)

5108-001

2007_598 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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35 participants in 11 patient groups

MK-5108 200 mg BID (Panel 1)

Experimental group

Description:

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).

Treatment:

Drug: MK-5108

MK-5108 400 mg BID (Panel 1)

Experimental group

Description:

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).

Treatment:

Drug: MK-5108

MK-5108 800 mg BID (Panel 1)

Experimental group

Description:

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).

Treatment:

Drug: MK-5108

MK-5108 1200 mg BID (Panel 1)

Experimental group

Description:

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).

Treatment:

Drug: MK-5108

MK-5108 1500 mg BID (Panel 1)

Experimental group

Description:

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).

Treatment:

Drug: MK-5108

MK-5108 1800 mg BID (Panel 1)

Experimental group

Description:

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).

Treatment:

Drug: MK-5108

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

Experimental group

Description:

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.

Treatment:

Drug: MK-5108

Drug: docetaxel

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

Experimental group

Description:

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.

Treatment:

Drug: MK-5108

Drug: docetaxel

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

Experimental group

Description:

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.

Treatment:

Drug: MK-5108

Drug: docetaxel

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

Experimental group

Description:

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.

Treatment:

Drug: MK-5108

Drug: docetaxel

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

Experimental group

Description:

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.

Treatment:

Drug: MK-5108

Drug: docetaxel