- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01047007
A Dose Escalation Study of Adavosertib(MK1775) in Combination With 5-FU or 5-FU/CDDP in Patients With Advanced Solid Tumor (1775-005
August 31, 2023 updated by: Merck Sharp & Dohme LLC
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
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 Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
11
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
20 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
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: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part 1: adavosertib 65 mg BID
Participants received 65 mg of adavosertib administered orally twice a day (BID) on Days 1-5 of a 21-day cycle.
|
Adavosertib 65 mg capsule administered orally on days 1-5 of a 21 day cycle.
Other Names:
|
Experimental: Part 2 A1: adavosertib 20 mg BID+5-FU 1000 mg
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.
|
5-FU 1000 mg/m^2/day administered as an intravenous (IV) infusion on Days 1-4 of a 21-day cycle
Adavosertib 20 mg capsule administered orally on days 1-5 of a 21 day cycle.
Other Names:
|
Experimental: Part 2 A2: adavosertib 20 mg QD+5-FU 1000 mg
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.
|
5-FU 1000 mg/m^2/day administered as an intravenous (IV) infusion on Days 1-4 of a 21-day cycle
Adavosertib 20 mg capsule administered orally on days 1-5 of a 21 day cycle.
Other Names:
|
Experimental: Parts 2B +3: adavosertib+5-FU+CDDP
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.
|
5-FU 1000 mg/m^2/day administered as an intravenous (IV) infusion on Days 1-4 of a 21-day cycle
CDDP 60 mg/m^2 to 100 mg/m^2 administered as an IV infusion on Day 1.
Other Names:
Adavosertib 65 mg capsule administered orally on days 1-5 of a 21 day cycle.
Other Names:
Adavosertib 20 mg capsule administered orally on days 1-5 of a 21 day cycle.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Cycle 1 (21 days)
|
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.
|
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
Time Frame: Cycle 1 (21 days)
|
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.
|
Cycle 1 (21 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MTD of MK1775 in Combination With 5-FU/CDDP Determined by Number of DLTs Per Dose Level: Locally Advanced or Metastatic Solid Tumors
Time Frame: Cycle 1 (21 days)
|
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.
|
Cycle 1 (21 days)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Medical Monitor, 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.
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)
January 18, 2010
Primary Completion (Actual)
June 15, 2011
Study Completion (Actual)
June 15, 2011
Study Registration Dates
First Submitted
January 11, 2010
First Submitted That Met QC Criteria
January 11, 2010
First Posted (Estimated)
January 12, 2010
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
- 1775-005
- MK1775-005 (Other Identifier: Merck Registration 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
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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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