Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Stomach Neoplasms

Head and Neck Neoplasms

Esophageal Cancer

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Fluorouracil

Cisplatin

Adavosertib

Enzyme Inhibitors

Participants received 65 mg of adavosertib administered orally twice a day (BID) on Days 1-5 of a 21-day cycle.

Participants received 20 mg of adavosertib administered orally BID on Days 1-5 of a 21-day cycle and 1000 mg/m\^2/day of 5-FU administered as an intravenous (IV) infusion on Days 1-4 of a 21-day cycle.

Participants received 20 mg of adavosertib administered orally once a day (QD) on Days 1-5 of a 21-day cycle and 1000 mg/m\^2/day of 5-FU administered as an IV infusion on Days 1-4 of a 21-day cycle.

Participants were to receive 20 mg or 65 mg of adavosertib administered either BID or QD on Days 1-5 of a 21-day cycle; 1000 mg/m\^2/day of 5-FU administered as an IV infusion on Days 1-4 of a 21-day cycle; and 60 mg/m\^2 to 100 mg/m\^2 of CDDP administered as an IV infusion on Day 1.

Adavosertib 20 mg capsule administered orally on days 1-5 of a 21 day cycle.

adavosertib 20 mg

5-FU 1000 mg/m\^2/day administered as an intravenous (IV) infusion on Days 1-4 of a 21-day cycle

5-FU 1000 mg/m^2/day

CDDP 60 mg/m\^2 to 100 mg/m\^2 administered as an IV infusion on Day 1.

CDDP

Adavosertib 65 mg capsule administered orally on days 1-5 of a 21 day cycle.

adavosertib 65 mg

Medical Monitor

The study evaluates safety of adavosertib in monotherapy, and in combination with 5-Fluorouracil (5-FU) alone or with 5-FU/cis-diamminedichloroplatinum (CDDP) in Japanese participants with solid tumor. The primary hypothesis is that adavosertib is safe and tolerable in participants with locally advanced or metastatic solid tumors.

A Dose Escalation Study of Adavosertib(MK1775) in Combination With 5-FU or 5-FU/CDDP in Patients With Advanced Solid Tumor (1775-005

A Phase I Dose Escalation Study of MK1775 in Monotherapy, in Combination With 5-Fluorouracil, and in Combination With 5-Fluorouracil and Cisplatin in Patients With Advanced Solid Tumor

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

DLT was defined using National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 and included: any drug-related hematologic toxicity ≥Grade 4 with the exception of Grade 4 neutropenia \<7 days duration; Grade 3 or 4 neutropenia with fever \>38.5 degrees Celsius and/or infection or neutropenia requiring colony-stimulating factor OR non-hematologic DLTs that were any Grade 3, 4, or 5 toxicity with the following exceptions: Grade 3 nausea, vomiting, diarrhea, and dehydration occurring in a setting of inadequate treatment; inadequately treated hypersensitivity reactions; Grade 3 elevated transaminases or urine electrolyte abnormality ≤1 week in duration; Grade 3 serum electrolyte abnormality ≤72 hours in duration. DLTs also included: drug-related adverse experience that lead to a dose modification; unresolved drug-related toxicity preventing treatment for ≥3 weeks or preventing administration of ≥8 of 10 doses in Parts 1 or 2A1 or 4 of 5 doses in Part 2A2.

The maximum tolerated dose (MTD) of MK-1775 in combination with 5-FU/CDDP for participants with locally advanced or metastatic esophageal, head and neck, or gastric cancer was determined based on DLTs that occurred during Cycle 1 of Parts 2B and 3. The MTD for MK-1775 in combination with 5-FU/CDDP was defined as the dose level at which approximately 30% of the participants were expected to experience a DLT for the combination therapy. The study was terminated early and Parts 2B and 3 were not performed. No participants received the 5-FU/CDDP regimen therefore the MTD for MK-1775 in combination with 5-FU/CDDP was not established.

The maximum tolerated dose (MTD) of MK-1775 in combination with 5-FU/CDDP for participants with locally advanced or metastatic solid tumors was determined based on DLTs that occurred during Cycle 1 of Parts 2B and 3. The MTD for MK-1775 in combination with 5-FU/CDDP was defined as the dose level at which approximately 30% of the participants were expected to experience a DLT for the combination therapy. The study was terminated early and Parts 2B and 3 were not performed. No participants received the 5-FU/CDDP regimen therefore the MTD for MK-1775 in combination with 5-FU/CDDP was not established.

Merck Sharp & Dohme LLC

AEs for all participants who received at least one dose of MK-1775 alone or in combination with 5-FU.

Participants received 65 mg of MK-1775 administered orally twice a day (BID) on Days 1-5 of a 21-day cycle.

Part 1: MK-1775 65 mg BID

Participants received 20 mg of MK-1775 administered orally BID on Days 1-5 of a 21-day cycle and 1000 mg/m\^2/day of 5-FU administered as an intravenous (IV) infusion on Days 1-4 of a 21-day cycle.

Part 2 A1: MK-1775 20 mg BID + 5-FU 1000 mg

Participants received 20 mg of MK-1775 administered orally once a day (QD) on Days 1-5 of a 21-day cycle and 1000 mg/m\^2/day of 5-FU administered as an IV infusion on Days 1-4 of a 21-day cycle.

Part 2 A2: MK-1775 20 mg QD + 5-FU 1000 mg

Participants were to receive 20 mg or 65 mg of MK-1775 administered either BID or QD on Days 1-5 of a 21-day cycle; 1000 mg/m\^2/day of 5-FU administered as an IV infusion on Days 1-4 of a 21-day cycle; and 60 mg/m\^2 to 100 mg/m\^2 of CDDP administered as an IV infusion on Day 1.

Parts 2B +3: MK-1775 + 5-FU + CDDP

Total

Age, Continuous

Sex: Female, Male

ECOG Score = 0

ECOG Score = 1

The ECOG scale of performance status is a measurement of how the disease impacts the daily living abilities of the participant. It describes a participant's level of functioning in terms of their ability to care for themself, daily activity, and physical ability. The scale ranges from 0 (fully active) to 5 (dead). The study required participants to have a score of 0 (fully active, able to carry on all pre-disease performance without restriction) or 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature).

ECOG Performance Status

The study required participants to have a solid tumor that failed to respond to standard therapy or progressed despite standard therapy as demonstrated by the number of prior chemotherapy regimens received.

Number of Prior Chemotherapy Regimens

Study terminated due to business reasons. Study Parts 2B and 3 were not done.

Senior Vice President, Global Clinical Development

The DLT-evaluable population consisted of participants who received at least one dose of MK-1775 and completed Cycle 1 of Parts 1, 2A1, 2A2, or discontinued due to toxicity.

Number of Participants With Dose Limiting Toxicities (DLTs)

Participants who received at least one dose of MK-1775 in combination with 5-FU/CDDP and completed Cycle 1 of Parts 2B and 3. No participants received the 5-FU/CDDP regimen due to early termination of the study.

Maximum Tolerated Dose (MTD) of MK1775 in Combination With 5-FU/CDDP Determined by Number of DLTs Per Dose Level: Locally Advanced or Metastatic Esophageal, Head and Neck, or Gastric Cancer

Spots Global Cancer Trial Database for A Dose Escalation Study of Adavosertib(MK1775) in Combination With 5-FU or 5-FU/CDDP in Patients With Advanced Solid Tumor (1775-005

Trial Identification

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Interventions

Study Description

Keywords

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