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

NCT01047007 | Terminated Phase 1 Results

• 2 other identifiers: 1775-005MK1775-005
• Study Type: interventional
• Target: 11
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Solid Tumors

Keywords

Head and Neck Cancer; Esophageal Cancer; Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Cycle 1 (21 days)

Secondary Outcomes (1)

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

  Cycle 1 (21 days)

Study Arms (4)

Part 1: adavosertib 65 mg BID

EXPERIMENTAL

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

Drug: adavosertib 65 mg

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

EXPERIMENTAL

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.

Drug: adavosertib 20 mg; Drug: 5-FU 1000 mg/m^2/day

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

EXPERIMENTAL

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.

Drug: adavosertib 20 mg; Drug: 5-FU 1000 mg/m^2/day

Parts 2B +3: adavosertib+5-FU+CDDP

EXPERIMENTAL

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.

Drug: adavosertib 20 mg; Drug: 5-FU 1000 mg/m^2/day; Drug: CDDP; Drug: adavosertib 65 mg

Interventions

adavosertib 20 mg DRUG

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

Also known as: MK-1775

Part 2 A1: adavosertib 20 mg BID+5-FU 1000 mg; Part 2 A2: adavosertib 20 mg QD+5-FU 1000 mg; Parts 2B +3: adavosertib+5-FU+CDDP

5-FU 1000 mg/m^2/day DRUG

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

Part 2 A1: adavosertib 20 mg BID+5-FU 1000 mg; Part 2 A2: adavosertib 20 mg QD+5-FU 1000 mg; Parts 2B +3: adavosertib+5-FU+CDDP

CDDP DRUG

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

Also known as: Cisplatin

Parts 2B +3: adavosertib+5-FU+CDDP

adavosertib 65 mg DRUG

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

Also known as: MK-1775

Part 1: adavosertib 65 mg BID; Parts 2B +3: adavosertib+5-FU+CDDP

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Head and Neck Neoplasms; Esophageal Neoplasms; Stomach Neoplasms

Interventions

adavosertib; Fluorouracil; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Limitations and Caveats

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

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2010
• First Posted: January 12, 2010
• Study Start: January 18, 2010
• Primary Completion: June 15, 2011
• Study Completion: June 15, 2011
• Last Updated: September 21, 2023
• Results First Posted: July 17, 2018

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share