A Phase 1 interventional study of adavosertib 20 mg and 5-FU 1000 mg/m^2/day in Solid Tumors, sponsored by Merck Sharp & Dohme LLC. Terminated. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2023-09-21.
Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment
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.
9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.
This study's enrollment of 11 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.
Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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
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
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
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
Adavosertib 20 mg capsule administered orally on days 1-5 of a 21 day cycle.
Also known as: MK-1775
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.
Also known as: Cisplatin
Adavosertib 65 mg capsule administered orally on days 1-5 of a 21 day cycle.
Also known as: MK-1775
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)
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.
Time frame: Cycle 1 (21 days)
This study enrolled participants with a 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 with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Additional inclusion and exclusion criteria applied.
| Milestone | Part 1: MK-1775 65 mg BID | Part 2 A1: MK-1775 20 mg BID + 5-FU 1000 mg | Part 2 A2: MK-1775 20 mg QD + 5-FU 1000 mg | Parts 2B +3: MK-1775 + 5-FU + CDDP |
|---|---|---|---|---|
| Started | 3 | 6 | 2 | 0 |
| Treated | 3 | 6 | 2 | 0 |
| Completed | 1 | 0 | 0 | 0 |
| Not completed | 2 | 6 | 2 | 0 |
| Withdrew: Adverse event | 0 | 2 | 1 | 0 |
| Withdrew: Progressive disease | 2 | 4 | 1 | 0 |
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.
| Participants | Part 1: MK-1775 65 mg BID | Part 2 A1: MK-1775 20 mg BID + 5-FU 1000 mg | Part 2 A2: MK-1775 20 mg QD + 5-FU 1000 mg | Parts 2B +3: MK-1775 + 5-FU + CDDP |
|---|---|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | 0 | 1 | 1 | — |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
Collected over From first dose of MK-1775 alone or in combination with 5-FU through follow-up; up to 7 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1: MK-1775 65 mg BID | — | 0/3 (0%) | 3/3 (100%) |
| Part 2 A1: MK-1775 20 mg BID + 5-FU 1000 mg | — | 2/6 (33.3%) | 6/6 (100%) |
| Part 2 A2: MK-1775 20 mg QD + 5-FU 1000 mg | — | 1/2 (50%) | 1/2 (50%) |
| Event | Part 1: MK-1775 65 mg BID | Part 2 A1: MK-1775 20 mg BID + 5-FU 1000 mg | Part 2 A2: MK-1775 20 mg QD + 5-FU 1000 mg |
|---|---|---|---|
| Gastric cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/3 | 0/6 | 1/2 |
| EncephalopathyNervous system disorders | 0/3 | 1/6 | 0/2 |
| Pulmonary fistulaRespiratory, thoracic and mediastinal disorders | 0/3 | 1/6 | 0/2 |
| Event | Part 1: MK-1775 65 mg BID | Part 2 A1: MK-1775 20 mg BID + 5-FU 1000 mg | Part 2 A2: MK-1775 20 mg QD + 5-FU 1000 mg |
|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 0/3 | 4/6 | 0/2 |
| DiarrhoeaGastrointestinal disorders | 2/3 | 3/6 | 0/2 |
| NauseaGastrointestinal disorders | 1/3 | 4/6 | 1/2 |
| StomatitisGastrointestinal disorders | 2/3 | 3/6 | 1/2 |
| VomitingGastrointestinal disorders | 0/3 | 4/6 | 0/2 |
| FatigueGeneral disorders | 1/3 | 4/6 | 1/2 |
| Decreased appetiteMetabolism and nutrition disorders | 0/3 | 4/6 | 1/2 |
| LymphopeniaBlood and lymphatic system disorders | 0/3 | 3/6 | 1/2 |
| NasopharyngitisInfections and infestations | 0/3 | 0/6 | 1/2 |
| Procedural painInjury, poisoning and procedural complications | 0/3 | 0/6 | 1/2 |
| Age, Continuous(Years) | Part 1: MK-1775 65 mg BID | Part 2 A1: MK-1775 20 mg BID + 5-FU 1000 mg | Part 2 A2: MK-1775 20 mg QD + 5-FU 1000 mg | Parts 2B +3: MK-1775 + 5-FU + CDDP | Total |
|---|---|---|---|---|---|
| Mean | 63.0 ± 4.4 | 62.7 ± 7.9 | 59.0 ± 5.7 | — | 62.1 ± 6.4 |
| Sex: Female, Male(Participants) | Part 1: MK-1775 65 mg BID | Part 2 A1: MK-1775 20 mg BID + 5-FU 1000 mg | Part 2 A2: MK-1775 20 mg QD + 5-FU 1000 mg | Parts 2B +3: MK-1775 + 5-FU + CDDP | Total |
|---|---|---|---|---|---|
| Female | 0 | 1 | 0 | — | 1 |
| Male | 3 | 5 | 2 | — | 10 |
| ECOG Performance Status(Participants) | Part 1: MK-1775 65 mg BID | Part 2 A1: MK-1775 20 mg BID + 5-FU 1000 mg | Part 2 A2: MK-1775 20 mg QD + 5-FU 1000 mg | Parts 2B +3: MK-1775 + 5-FU + CDDP | Total |
|---|---|---|---|---|---|
| ECOG Score = 0 | 2 | 3 | 2 | — | 7 |
| ECOG Score = 1 | 1 | 3 | 0 | — | 4 |
| Number of Prior Chemotherapy Regimens(Prior regimens) | Part 1: MK-1775 65 mg BID | Part 2 A1: MK-1775 20 mg BID + 5-FU 1000 mg | Part 2 A2: MK-1775 20 mg QD + 5-FU 1000 mg | Parts 2B +3: MK-1775 + 5-FU + CDDP | Total |
|---|---|---|---|---|---|
| Mean | 2.0 ± 0.0 | 3.3 ± 0.8 | 4.0 ± 0.0 | — | 3.1 ± 0.9 |
No study locations are listed for this record.
Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
This study is terminated, as verified in Aug 2023. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Merck Sharp & Dohme LLC