A Dose Escalation Study of MK1775 in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adults With Advanced Solid Tumors (MK-1775-001 AM7) - Full Text View

Sponsor:	Merck
Information provided by (Responsible Party):	Merck
ClinicalTrials.gov Identifier:	NCT00648648

Purpose

This study will investigate MK1775 alone and in combination with one of the following three drugs: gemcitabine, cisplatin, and carboplatin in patients with advanced solid tumors. The purpose of the study is to test safety and tolerability of MK1775 alone and in combination, and to find the maximum tolerated dose (MTD) of MK1775 as monotherapy and in combination therapy.

Condition	Intervention	Phase
Solid Tumors	Drug: MK1775 Drug: gemcitabine Drug: cisplatin Drug: carboplatin	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Dose Escalation Study Evaluating MK1775 in Both Monotherapy and in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adult Subjects With Advanced Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Cisplatin Carboplatin Gemcitabine Gemcitabine hydrochloride

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Number of participants with dose limiting toxicities [ Time Frame: Cycle 1 (14 days for monotherapy and 21-28 days for combination therapy) ] [ Designated as safety issue: Yes ]
Change from baseline in biomarkers PHH3, CDC2, and pCDC2 [ Time Frame: At screening and Cycle 1 dependent upon tumor type ] [ Designated as safety issue: No ]
Plasma concentration of MK1775 [ Time Frame: Day 1 pre- and post-dose, Day 2, and Day 3 of Cycle 1 monotherapy, and Day 2 and 3 of combination therapy (optional at Days 4 and 5) ] [ Designated as safety issue: No ]
Urine concentration of MK-1775 [ Time Frame: Up to 24 hours post Day 1 dose of monotherapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of participants with objective response [ Time Frame: Tumor will be measured on the first day of every-other treatment cycle, or as clinically indicated ] [ Designated as safety issue: No ]

Estimated Enrollment:	155
Study Start Date:	February 2008
Estimated Study Completion Date:	July 2012
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Part 1: MK1775 single dose Part 1: MK1775 capsules will be given on Day 1 of a 14-day cycle: starting dose of MK1775 is 325 mg and will escalate up to 1300 mg or until MTD achieved	Drug: MK1775 Dose escalation study. Part 1: MK1775 capsules will be given on Day 1 of a 14-day cycle: starting dose of MK1775 is 325 mg and will escalate up to 1300 mg or until MTD achieved. Dose Levels for MK1775: 325 mg, 650 mg, and 1300 mg.
Experimental: Part 3: Confirmation and Expansion Part 3: Patients will be treated with MTD of MK1775 from Part 2-B in combination with the MTD from Part 2-B of either gemcitabine, cisplatin, or carboplatin.	Drug: MK1775 Part 3: consists of treatment with MTD of MK1775 from Part 2-B. Drug: gemcitabine gemcitabine - IV infusions dosage ranging from 1000 mg/m^2 to 600 mg/m^2 in a 28-day cycle. Drug: cisplatin cisplatin - IV infusion dosage ranging from 75 mg/m^2 to 50 mg/m^2 in a 21-day cycle. Drug: carboplatin carboplatin - IV infusion dosage ranging from AUC/time curve of 5 mg/min/mL to AUC 3 in a 21-day cycle.
Experimental: Part 2-A Gemcitabine Starting single dose of MK1775, 100 mg with gemcitabine IV infusions dosage ranging from 1000 mg/m^2 to 600 mg/m^2 in a 28-day cycle	Drug: gemcitabine gemcitabine - IV infusions dosage ranging from 1000 mg/m^2 to 600 mg/m^2 in a 28-day cycle. Dose Levels for Gemcitabine: 1000 mg/m^2, 800 mg/m^2, 600 mg/m^2 Drug: MK1775 Part 2-A: consists of three treatment arms, each combining a single starting dose of MK1775, 100 mg in a 21-28 day cycle. Dose Levels for MK1775: 50 mg, 100 mg, 200 mg, 325 mg, 475 mg, 675 mg, 900 mg, 1200 mg, 1600 mg (undetermined interim doses are allowed)
Experimental: Part 2-A Cisplatin Starting single dose of MK1775, 100 mg with cisplatin IV infusion dosage ranging from 75 mg/m^2 to 50 mg/m^2 in a 21-day cycle.	Drug: cisplatin cisplatin - IV infusion dosage ranging from 75 mg/m^2 to 50 mg/m^2 in a 21-day cycle. Dose Levels for cisplatin 75 mg/m^2, 60 mg/m^2, 50 mg/m^2 Drug: MK1775 Part 2-A: consists of three treatment arms, each combining a single starting dose of MK1775, 100 mg in a 21-28 day cycle. Dose Levels for MK1775: 50 mg, 100 mg, 200 mg, 325 mg, 475 mg, 675 mg, 900 mg, 1200 mg, 1600 mg (undetermined interim doses are allowed)
Experimental: Part 2-A Carboplatin Starting single dose of MK1775, 100 mg with carboplatin IV infusion dosage ranging from AUC/time curve of 5 mg/min/mL to AUC 3 in a 21-day cycle.	Drug: carboplatin carboplatin - IV infusion dosage ranging from AUC/time curve of 5 mg/min/mL to AUC 3 in a 21-day cycle. Dose levels for carboplatin: AUC 5, AUC 4, AUC 3 Drug: MK1775 Part 2-A: consists of three treatment arms, each combining a single starting dose of MK1775, 100 mg in a 21-28 day cycle. Dose Levels for MK1775: 50 mg, 100 mg, 200 mg, 325 mg, 475 mg, 675 mg, 900 mg, 1200 mg, 1600 mg (undetermined interim doses are allowed)
Experimental: Part 2-B Gemcitabine Starting multiple dose of MK1775, 50 mg with gemcitabine IV infusions dosage ranging from 1000 mg/m^2 to 600 mg/m^2 in a 28-day cycle	Drug: gemcitabine gemcitabine - IV infusions dosage ranging from 1000 mg/m^2 to 600 mg/m^2 in a 28-day cycle. Dose Levels for Gemcitabine: 1000 mg/m^2, 800 mg/m^2, 600 mg/m^2 Drug: MK1775 Part 2-B: consists of three treatment arms, each combining a starting dose of MK1775, 50 mg (for gemcitabine) in a 28 day cycle. Dose Levels for MK1775: 25 mg, 50 mg, 100 mg, 125 mg, 150 mg, 200 mg, 250 mg, 325 mg, 425 mg (undetermined interim doses are allowed)
Experimental: Part 2-B Cisplatin Starting multiple dose of MK1775, 50 mg with cisplatin IV infusion dosage ranging from 75 mg/m^2 to 50 mg/m^2 in a 21-day cycle	Drug: cisplatin cisplatin - IV infusion dosage ranging from 75 mg/m^2 to 50 mg/m^2 in a 21-day cycle. Dose Levels for cisplatin 75 mg/m^2, 60 mg/m^2, 50 mg/m^2 Drug: MK1775 Part 2-B: consists of three treatment arms, each combining a starting dose of MK1775, 50 mg (for gemcitabine) in a 28 day cycle. Dose Levels for MK1775: 25 mg, 50 mg, 100 mg, 125 mg, 150 mg, 200 mg, 250 mg, 325 mg, 425 mg (undetermined interim doses are allowed)
Experimental: Part 2-B Carboplatin Starting multiple dose of MK1775, 75 mg with cisplatin IV infusion dosage ranging from AUC/time curve of 5 mg/min/mL to AUC 3 in a 21-day cycle.	Drug: carboplatin carboplatin - IV infusion dosage ranging from AUC/time curve of 5 mg/min/mL to AUC 3 in a 21-day cycle. Dose levels for carboplatin: AUC 5, AUC 4, AUC 3 Drug: MK1775 Part 2-B: consists of three treatment arms, each combining a starting dose of MK1775, 50 mg (for gemcitabine) in a 28 day cycle. Dose Levels for MK1775: 25 mg, 50 mg, 100 mg, 125 mg, 150 mg, 200 mg, 250 mg, 325 mg, 425 mg (undetermined interim doses are allowed)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subject must have a histologically confirmed metastatic or locally advanced solid tumor, progressed despite standard therapy, or for which standard therapy does not exist
Subject is at least 18 years old
Subject must have performance status of <=1 on the ECOG Performance Scale
Female subjects must not be pregnant

Exclusion Criteria:

Subject has had chemotherapy, radiotherapy, or biological therapy within 4 weeks prior to entering the study or who has not recovered from adverse events due to agents given more than 4 weeks earlier
Subject is participating or has participated in a study with an investigational compound or device within 30 days
Subjects with active CNS metastases and/or carcinomatous meningitis are excluded. However, subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry
Subject with a primary central nervous system tumor
Subject is allergic to any of the components of the combination study therapy or its analogs
Participant has had prescription or non-prescription drugs or other products known to be metabolized by CYP3A4 that cannot be discontinued prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication. Medications of particular concern are inhibitors of CYP3A4 (azole antifungals [ketoconazole, itraconazole], macrolide antibiotics [erythromycin, clarithromycin], cimetidine, aprepitant, HIV protease inhibitors, nefrazodone, and the following inducers of CYP3A4: phenytoin, barbiturates and rifampicin, and substrates of CYP3A4 including statins (lovastatin, simvastatin), midazolam, terfenadine, astemizole, and cisapride
Subject is a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse
Subject is pregnant or breastfeeding, or expecting to get pregnant during the time the study will be ongoing
Subject is (HIV)-positive
Subject has a history of Hepatitis B or C
Subject has symptomatic ascites or pleural effusion. A subject who is clinically stable following treatment for these conditions is eligible
Subject must not have prior radiation therapy to more than 30% of the bone marrow and must have recovered for at least 3 weeks from the hematologic toxicity of prior radiotherapy
Subject has had a prior stem cell or bone marrow transplant
Subject has received more than 4 prior cytotoxic chemotherapy regimens
Participant has a history suggestive of Li-Fraumeni Syndrome

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00648648

Contacts

Contact: Toll Free Number

1-888-577-8839

Locations

Canada, Quebec
Merck Frosst Canada Ltd.	Recruiting
Kirkland, Quebec, Canada, H9H 3L1
Contact: Michel Cimon 514-428-2605
Netherlands
Merck Sharp & Dohme B.V.	Recruiting
Haarlem, Netherlands, 2031 BN
Contact: Caroline Doornebos 31-23-515-3362

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

No publications provided

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT00648648 History of Changes
Other Study ID Numbers:	2007_611, MK1775-001
Study First Received:	March 26, 2008
Last Updated:	December 2, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Neoplasms
Gemcitabine
Cisplatin
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on February 09, 2012