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

August 31, 2023 updated by: Merck Sharp & Dohme LLC

A Phase I Dose Escalation Study Evaluating MK-1775 in Both Monotherapy and in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adult Subjects With Advanced Solid Tumors

This study will investigate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) activity of adavosertib, both as monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in participants with advanced solid tumors. Dose limiting toxicities (DLT) of adavosertib in combination with gemcitabine, cisplatin, or carboplatin will also be assessed. The primary hypotheses of the study are as follows: 1) Oral administration of adavosertib both as monotherapy and in combination with either gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors will be safe and tolerable, 2) The side effects observed in participants with advanced solid tumors after administration of adavosertib combined with each of the chemotherapies (gemcitabine, cisplatin and carboplatin) will allow for the definition of a single dose combination Maximum Administered Dose (MAD)/Maximum Tolerated Dose (MTD) and a multiple dose combination Biologically Effective Dose (BED)/MTD for each of the 3 combinations, 3) At a tolerated dose, adavosertib plasma exposure will exceed target thresholds established in preclinical models, and 4) At a tolerated dose, PD markers of adavosertib activity in combination with either gemcitabine, cisplatin, or carboplatin (in surrogate tissue and/or tumor) will meet or exceed the target threshold established in preclinical models.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Part 1 consists of single dose adavosertib monotherapy. If well tolerated, participants in Part 1 will continue on to one of three treatment arms in Part 2-A which consists of a single lower dose of adavosertib in combination with standard chemotherapy: 1) Adavosertib +Gemcitabine (1000 mg/m^2), 2) Adavosertib + Cisplatin (75 mg/m^2) or 3) Adavosertib +Carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5). Following completion of Part 2-A, adavosertib will be administered twice daily (BID) for 2.5 days (multi-dose) starting concomitantly with each administration of chemotherapy in Part 2-B. After a preliminary combination MTD of adavosertib and chemotherapy has been established in Part 2B, the MTD confirmation expansion will occur in Part 3.

Study Type

Interventional

Enrollment (Actual)

206

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Must have a histologically confirmed metastatic or locally advanced solid tumor, progressed despite standard therapy, or for which standard therapy does not exist
  • Must have performance status of <=1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
  • Female participants must not be pregnant

Exclusion Criteria:

  • 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
  • Is participating or has participated in a study with an investigational compound or device within 30 days
  • Has active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, participants 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
  • Has a primary central nervous system tumor
  • 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 Cytochrome P450 3A4 (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, Human Immunodeficiency Virus (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
  • 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
  • Pregnant or breastfeeding, or expecting to get pregnant during the time the study will be ongoing
  • HIV-positive
  • History of Hepatitis B or C
  • Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions is eligible
  • Participant 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
  • Has had a prior stem cell or bone marrow transplant
  • Has received more than 4 prior cytotoxic chemotherapy regimens
  • Has a history suggestive of Li-Fraumeni Syndrome

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: adavosertib 325 mg Single Dose
Participants received adavosertib 325 mg, orally, on Day 1.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 650 mg Single Dose
Participants received adavosertib 650 mg, orally, on Day 1.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 1300 mg Single Dose
Participants received adavosertib 1300 mg, orally, on Day 1.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 100 mg Single Dose + Gemcitabine 1000 mg/m^2
Participants received gemcitabine 1000 mg/m^2 as an intravenous (IV) infusion on Days 1, 8, and 15 in each 4-week cycle plus adavosertib 100 mg single dose, orally, on Day 2 of each cycle.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 200 mg Single Dose + Gemcitabine 1000 mg/m^2
Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 in each 4-week cycle plus adavosertib 200 mg single dose, orally, on Day 2 of each cycle.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 100 mg Single Dose + Cisplatin 75 mg/ m^2
Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 100 mg single dose orally, on Day 2 of each cycle.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 200 mg Single Dose + Cisplatin 75 mg/ m^2
Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 200 mg single dose orally, on Day 2 of each cycle.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 100 mg Single Dose + Carboplatin AUC 5
Participants received carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5) as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 100 mg single dose orally, on Day 2 of each cycle.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 200 mg Single Dose + Carboplatin AUC 5
Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 200 mg single dose orally, on Day 2 of each cycle.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 325 mg Single Dose + Carboplatin AUC 5
Participants received carboplatin AUC5 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 325 mg single dose orally, on Day 2 of each cycle.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2
Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4-week cycle plus adavosertib 25 mg orally twice daily (BID) for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of adavosertib 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each cycle.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2
Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus adavosertib 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 doses of adavosertib 25 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2
Participants received gemcitabine 1000 mg/m^2 as an IV infusion given once weekly for 3 consecutive weeks of a 4 week cycle plus adavosertib 50 mg orally BID for 2.5 days, starting concomitantly with the IV infusion of gemcitabine on Day 1 and followed by 4 additional doses of adavosertib 50 mg at approximately 12 hour intervals on Days 1-3, 8-9, and 15-17 of each 4 week cycle.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2
Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus adavosertib 100 mg orally once daily (QD) on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2
Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus adavosertib 125 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2
Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus adavosertib 150 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2
Participants received gemcitabine 1000 mg/m^2 as an IV infusion given on Days 1, 8, and 15 of each 4 week cycle plus adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2
Participants received gemcitabine 1000 mg/m^2 as an IV infusion on Days 1, 8, and 15 of each 4 week cycle plus adavosertib 200 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of each 4 week cycle.
Drug: gemcitabine
Gemcitabine administered at 1000 mg/m^2 by IV infusion in a 28-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2
Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 50 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2
Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 100 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2
Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 125 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2
Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 150 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2
Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 200 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2
Participants received cisplatin 75 mg/ m^2 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 250 mg orally BID for 2.5 days, starting concomitantly with the administration of cisplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle.
Drug: cisplatin
Cisplatin administered at 75 mg/m^2 by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5
Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 75 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5
Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 150 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5
Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 225 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775
Experimental: adavosertib 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5
Participants received carboplatin AUC 5 as an IV infusion on Day 1 of each 3 week cycle plus adavosertib 325 mg orally BID for 2.5 days, starting concomitantly with the administration of carboplatin on Day 1 and then at 12 hour intervals on Days 1-3 of each 3 week cycle.
Drug: carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
Drug: adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
Other Names:
  • MK-1775

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Time Frame: Part 1: Up to 14 days, Part 2: Up to 28 days
DLTs were adverse events (AEs) considered at least possibly related to study drug that prevented escalation of the drug dose. Hematologic DLTs were any grade (Gr) 4-5 toxicity EXCEPT: Gr 4 anemia and Gr 4 leukopenia, Gr 4 neutropenia lasting for <7 days, Gr 4 thrombocytopenia lasting for <4 days except if a platelet transfusion is required, and Gr 3/Gr 4 neutropenia with fever >38.5°C and/or infection requiring antibiotic or anti-fungal treatment. Non-hematologic DLT was defined as any Gr 3, 4, or 5 non-hematologic toxicity EXCEPT: nausea, vomiting, diarrhea, or dehydration (all Gr 3) occurring in a setting of inadequate compliance with supportive care measures and lasting for <48 hours, alopecia of any grade, inadequately treated hypersensitivity reactions, and clinically non-significant, treatable or reversible lab abnormalities including liver function tests, uric acid, etc.
Part 1: Up to 14 days, Part 2: Up to 28 days
Percentage of Total Cyclin-dependent Kinase (CDC2)-Positive Cells That Were Phosphorylated (pCDC2) in Skin Cells at Baseline and 8 Hours After MK-1775 Dosing
Time Frame: Baseline, 8 hours after first MK-1775 dose
The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total CDC2-positive cells that were pCDC2 positive (% pCDC2-positive cells) at baseline and 8 hours after MK-1775 dosing were reported for participants in Part 1, 2-A, and 2-B/3 treatment groups with available data per protocol.
Baseline, 8 hours after first MK-1775 dose
Percentage of Total pCDC2 in Skin Cells at Baseline and 24 Hours After MK-1775 Dosing
Time Frame: Baseline, 24 hours after first MK-1775 dose
The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total pCDC2 at baseline and 24 hours after MK-1775 dosing were reported for participants in the Part 2-B/3 MK-1775 QD x2 Multi Dose plus Gemcitabine treatment groups with available data per protocol.
Baseline, 24 hours after first MK-1775 dose
Percentage of Total pCDC2 in Skin Cells at Baseline and 48 Hours After MK-1775 Dosing
Time Frame: Baseline, 48 hours after first MK-1775 dose
The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total pCDC2 at baseline and at 48 hours after MK-1775 dosing were reported for participants in the Part 2-B/3 MK-1775 (150 mg, 200 mg, 250) BID x 2.5 Multi Dose plus cisplatin 75 mg/m^2 groups and the 325 mg BID x2.5 Multi Dose + Carboplatin group with available data per protocol.
Baseline, 48 hours after first MK-1775 dose
Plasma Concentration of MK-1775 at 8 Hours After Administration (C8hr) of Single or Multiple Oral Doses
Time Frame: 8 hours after MK-1775 dose
MK-1775 was measured in the plasma at 8 hours after dosing (Day 1 for single dose of monotherapy, Day 2 of single-dose combination therapy and QD x 2 Combination dosing, and Day 3 dose for BID X 2.5 combination dosing) for participants with available data.
8 hours after MK-1775 dose
Mean Urine Excretion of MK-1775 24 Hours After the Day 1 Monotherapy Dose
Time Frame: At 0-4 hours, 4-8 hours, and 12-24 hours post Day 1 dose of monotherapy
The mean cumulative amount of MK-1775 excreted unchanged in urine after a single oral dose was measured during the initial monotherapy cycle of the study. For this outcome measure, samples were collected and analyzed only for the MK-1775 monotherapy arms of the study at defined intervals after the Day 1 dose of monotherapy. Part 2 MK-1775 combination arms were not sampled per protocol.
At 0-4 hours, 4-8 hours, and 12-24 hours post Day 1 dose of monotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Overall Response as Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Time Frame: From Day 1 up through discontinuation of study treatment (up to ~11.2 months)
Best overall response achieved by a participant. Starting at Day 1, participants in Part 2 were evaluated for tumor response every 6-8 weeks until discontinuation from study treatment according to RECIST criteria; which are based on radiographic imaging. Recorded responses were either confirmed by Central Review or unconfirmed (Investigator assessment only), and included complete response (CR; defined as disappearance of all target lesions), partial response (PR; at least a 30% decrease in the sum of the longest diameter [LD] of target lesions, taking as reference the baseline sum LD), stable disease (SD; neither sufficient shrinkage to qualify for PR nor sufficient growth to qualify for PD, taking as reference the smallest sum LD since the treatment started), or progressive disease (PD; ≥20% increase in sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions).
From Day 1 up through discontinuation of study treatment (up to ~11.2 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 25, 2008

Primary Completion (Actual)

January 6, 2014

Study Completion (Actual)

January 6, 2014

Study Registration Dates

First Submitted

March 26, 2008

First Submitted That Met QC Criteria

March 28, 2008

First Posted (Estimated)

April 1, 2008

Study Record Updates

Last Update Posted (Actual)

September 21, 2023

Last Update Submitted That Met QC Criteria

August 31, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1775-001
  • 2007_611 (Other Identifier: Merck Registration Number)
  • 2007-005304-40 (EudraCT Number)
  • MK-1775-001 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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