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)
NCT ID: NCT00648648
Last Updated: 2023-09-21
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1
206 participants
INTERVENTIONAL
2008-02-25
2014-01-06
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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adavosertib 325 mg Single Dose
Participants received adavosertib 325 mg, orally, on Day 1.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
adavosertib 650 mg Single Dose
Participants received adavosertib 650 mg, orally, on Day 1.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
adavosertib 1300 mg Single Dose
Participants received adavosertib 1300 mg, orally, on Day 1.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
gemcitabine
Gemcitabine administered at 1000 mg/m\^2 by IV infusion in a 28-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
gemcitabine
Gemcitabine administered at 1000 mg/m\^2 by IV infusion in a 28-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
cisplatin
Cisplatin administered at 75 mg/m\^2 by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
cisplatin
Cisplatin administered at 75 mg/m\^2 by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
gemcitabine
Gemcitabine administered at 1000 mg/m\^2 by IV infusion in a 28-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
gemcitabine
Gemcitabine administered at 1000 mg/m\^2 by IV infusion in a 28-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
gemcitabine
Gemcitabine administered at 1000 mg/m\^2 by IV infusion in a 28-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
gemcitabine
Gemcitabine administered at 1000 mg/m\^2 by IV infusion in a 28-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
gemcitabine
Gemcitabine administered at 1000 mg/m\^2 by IV infusion in a 28-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
gemcitabine
Gemcitabine administered at 1000 mg/m\^2 by IV infusion in a 28-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
gemcitabine
Gemcitabine administered at 1000 mg/m\^2 by IV infusion in a 28-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
gemcitabine
Gemcitabine administered at 1000 mg/m\^2 by IV infusion in a 28-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
cisplatin
Cisplatin administered at 75 mg/m\^2 by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
cisplatin
Cisplatin administered at 75 mg/m\^2 by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
cisplatin
Cisplatin administered at 75 mg/m\^2 by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
cisplatin
Cisplatin administered at 75 mg/m\^2 by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
cisplatin
Cisplatin administered at 75 mg/m\^2 by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
cisplatin
Cisplatin administered at 75 mg/m\^2 by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
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.
adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
Interventions
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adavosertib
adavosertib administered as an oral formulation as either monotherapy or in combination with either gemcitabine, cisplatin, or carboplatin.
gemcitabine
Gemcitabine administered at 1000 mg/m\^2 by IV infusion in a 28-day cycle.
cisplatin
Cisplatin administered at 75 mg/m\^2 by IV infusion in a 21-day cycle.
carboplatin
Carboplatin administered at AUC/time curve of 5 mg/min/mL (AUC5) by IV infusion in a 21-day cycle.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Must have performance status of \<=1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
* Female participants must not be pregnant
Exclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
References
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Leijen S, van Geel RM, Pavlick AC, Tibes R, Rosen L, Razak AR, Lam R, Demuth T, Rose S, Lee MA, Freshwater T, Shumway S, Liang LW, Oza AM, Schellens JH, Shapiro GI. Phase I Study Evaluating WEE1 Inhibitor AZD1775 As Monotherapy and in Combination With Gemcitabine, Cisplatin, or Carboplatin in Patients With Advanced Solid Tumors. J Clin Oncol. 2016 Dec 20;34(36):4371-4380. doi: 10.1200/JCO.2016.67.5991. Epub 2016 Oct 31.
Related Links
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Merck Clinical Trials Information
Other Identifiers
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2007_611
Identifier Type: OTHER
Identifier Source: secondary_id
MK-1775-001
Identifier Type: OTHER
Identifier Source: secondary_id
2007-005304-40
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
1775-001
Identifier Type: -
Identifier Source: org_study_id
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