Treatment of Participants With Advanced and/or Refractory... | NCT00543387

ID	Type	Description	Link
2007_598	Other Identifier	Sponsor Registry Number
MK-5108-001	Other Identifier	Merck Protocol Number

Treatment of Participants With Advanced and/or Refractory... | NCT00543387 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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).

Interventions

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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)

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26620496	Result	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.

Arm/Group Information

ID	Title	Description
FG000	MK-5108 200 mg BID (Panel 1)	Participants received 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).
FG001	MK-5108 400 mg BID (Panel 1)	Participants received 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).
FG002	MK-5108 800 mg BID (Panel 1)	Participants received 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).
FG003	MK-5108 1200 mg BID (Panel 1)	Participants received 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).
FG004	MK-5108 1500 mg BID (Panel 1)	Participants received 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).
FG005	MK-5108 1800 mg BID (Panel 1)	Participants received 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).
FG006	MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Panel 2)	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.
FG007	MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Panel 2)	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.
FG008	MK-5108 225 mg BID + 60 mg/m^2 Docetaxel (Panel 2)	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.
FG009	MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Crossover)	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.
FG010	MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Crossover)	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.

Periods

Title

Milestones

Reasons Not Completed

Panel 1 + Panel 2

Type	Comment	Milestone Data
STARTED		FG0003 subjects FG0013 subjects FG0023 subjects FG0033 subjects FG0043 subjects FG0053 subjects FG0066 subjects FG0076 subjects FG0085 subjects FG0090 subjects FG0100 subjects
Crossed Over to Panel 2 Due to PD		FG0000 subjects FG0011 subjects FG0020 subjects FG0030 subjects FG004
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
NOT COMPLETED		FG0003 subjects FG0013 subjects FG0023 subjects FG0033 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0011 subjects FG0020 subjects FG003

Crossover Participants

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	MK-5108 200 mg BID (Panel 1)	Participants received 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).
BG001	MK-5108 400 mg BID (Panel 1)

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

All participants that received one or more doses of study medication. Four participants who received MK-5108 monotherapy in Panel 1 and then crossed over to receive combination treatment in Panel 2 (Crossover) were included in both respective treatment groups and AEs were reported according to treatment received.

Posted

Count of Participants

Participants

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

ID	Title	Description

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MK-5108 200 mg BID (Panel 1)	Participants received 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).

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Senior Vice President, Global Clinical Development	Merck Sharp & Dohme Corp.	1-800-672-6372		ClinicalTrialsDisclosure@merck.com

ID	Term
D009369	Neoplasms

Intervention Browse Module

ID	Term
C547876	4-(3-chloro-2-fluorophenoxy)-1-((6-(1,3-thiazol-2-ylamino)pyridin to 2-yl)methyl) cyclohexanecarboxylic acid
D000077143	Docetaxel

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic

Type	Comment	Reasons
Progressive Disease		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG0040 subjects FG0050 subjects FG0060 subjects FG0070 subjects FG0080 subjects FG0091 subjects FG0102 subjects
Study Terminated by Sponsor		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Primary

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.

All participants that received one or more doses of study medication. Participants who received MK-5108 monotherapy in Panel 1 and then crossed over to receive combination treatment in Panel 2 (Crossover) were included in both respective treatment groups and DLTs were reported according to treatment received.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	MK-5108 200 mg BID (Panel 1)	Participants received 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).
OG001	MK-5108 400 mg BID (Panel 1)	Participants received 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).
OG002	MK-5108 800 mg BID (Panel 1)	Participants received 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).
OG003	MK-5108 1200 mg BID (Panel 1)	Participants received 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).
OG004	MK-5108 1500 mg BID (Panel 1)	Participants received 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).
OG005	MK-5108 1800 mg BID (Panel 1)	Participants received 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).
OG006	MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Panel 2)	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.
OG007	MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Panel 2)	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.
OG008	MK-5108 225 mg BID + 60 mg/m^2 Docetaxel (Panel 2)	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.
OG009	MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Crossover)	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.
OG010	MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Crossover)	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.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators