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

Phase 1TerminatedNCT01047007

Merck Sharp & Dohme LLC11 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumors

Interventions

adavosertib 20 mgDRUG

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

5-FU 1000 mg/m^2/dayDRUG

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

CDDPDRUG

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

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Parts 1 and 2-A: Patient must have a histologically or cytologically confirmed locally advanced or metastatic solid tumor failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist * Parts 2-B and 3: Patient must have a histologically or cytologically confirmed locally advanced or metastatic esophageal, head and neck, or gastric cancer, and be a candidate of 5-Fluorouracil and Cisplatin regimen defined in this study * Patient must have performance status of 0 or 1 on the ECOG Performance Scale Exclusion Criteria: * Patient who has had chemotherapy, radiotherapy, or biological therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the first dose of study drug or who has not recovered from adverse events due to agents administered more than 4 weeks earlier * Patient with a known primary central nervous system tumor * Patient has known hypersensitivity to any of the components of the combination study therapy or its analogs * Patient is receiving "alternative" cancer medications such as plant-derived products and their analogs with anti-tumor activity within 1 week prior to entering the study. * Patient 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

Outcomes

Primary Outcomes

Number of Participants With Dose Limiting Toxicities (DLTs)

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.

Time frame: Cycle 1 (21 days)

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

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.

Time frame: Cycle 1 (21 days)

Secondary Outcomes

MTD of MK1775 in Combination With 5-FU/CDDP Determined by Number of DLTs Per Dose Level: Locally Advanced or Metastatic Solid Tumors

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.

Data from ClinicalTrials.gov

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