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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00648648
First received: March 26, 2008
Last updated: January 29, 2014
Last verified: January 2014

March 26, 2008
January 29, 2014
February 2008
January 2014   (final data collection date for primary outcome measure)
  • 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 ]
Dose limiting toxicities; maximum tolerated dose; predictive biomarkers; plasma and urine concentrations of MK1775 and metabolites [ Time Frame: Study will continue until dose limiting toxicity and/or maximum tolerated dose is reached. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00648648 on ClinicalTrials.gov Archive Site
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 ]
Disease progression; biologically effective dose [ Time Frame: Tumor progression will be measured on first day of every treatment cycle ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Dose Escalation Study of MK1775 in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adults With Advanced Solid Tumors (MK-1775-001 AM7)
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

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Solid Tumors
  • 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.
  • 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: 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: 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)
  • 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)
  • 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 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
    Intervention: Drug: MK1775
  • 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.
    Interventions:
    • Drug: MK1775
    • Drug: gemcitabine
    • Drug: cisplatin
    • Drug: carboplatin
  • 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
    Interventions:
    • Drug: gemcitabine
    • Drug: MK1775
  • 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.
    Interventions:
    • Drug: cisplatin
    • Drug: MK1775
  • 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.
    Interventions:
    • Drug: carboplatin
    • Drug: MK1775
  • 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
    Interventions:
    • Drug: gemcitabine
    • Drug: MK1775
  • 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
    Interventions:
    • Drug: cisplatin
    • Drug: MK1775
  • 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.
    Interventions:
    • Drug: carboplatin
    • Drug: MK1775
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
203
January 2014
January 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00648648
1775-001, 2007_611
No
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP