Trial · NCT00648648
A Dose Escalation Study of Adavosertib (MK-1775) in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adults With Advanced Solid Tumors (MK-1775-001)
NCT00648648, Phase 1, Completed, Merck Sharp & Dohme LLC; results first posted 2019-04-05
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Dose Escalation Study of Adavosertib (MK-1775) in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adults With Advanced Solid Tumors (MK-1775-001). Trials, record NCT00648648. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT00648648
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Dose Escalation Study of Adavosertib (MK-1775) in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adults With Advanced Solid Tumors (MK-1775-001)
- NCT number
- NCT00648648
- Status
- Completed
- Phases
- Phase 1
- Enrollment
- 206 participants, actual
- Lead sponsor
- Merck Sharp & Dohme LLC
- Conditions
- Solid Tumors
- Interventions
- adavosertib, gemcitabine, cisplatin, carboplatin
- First posted
- 2008-04-01
- Last updated
- 2023-09-21
- Other registries' IDs
- eudract:2007-005304-40
- Results first posted
- 2019-04-05
Source ClinicalTrials.gov
Registered outcomes7
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | Part 1: Up to 14 days, Part 2: Up to 28 days | DLTs were adverse events (AEs) considered at least possibly related to study drug that prevented escalation of the drug dose. Hematologic DLTs were any grade (Gr) 4-5 toxicity EXCEPT: Gr 4 anemia and Gr 4 leukopenia, Gr 4 neutropenia lasting for \<7 days, Gr 4 thrombocytopenia lasting for \<4 days except if a platelet transfusion is required, and Gr 3/Gr 4 neutropenia with fever \>38.5°C and/or infection requiring antibiotic or anti-fungal treatment. Non-hematologic DLT was defined as any Gr 3, 4, or 5 non-hematologic toxicity EXCEPT: nausea, vomiting, diarrhea, or dehydration (all Gr 3) occurring in a setting of inadequate compliance with supportive care measures and lasting for \<48 hours, alopecia of any grade, inadequately treated hypersensitivity reactions, and clinically non-significant, treatable or reversible lab abnormalities including liver function tests, uric acid, etc. |
| Primary | Percentage of Total Cyclin-dependent Kinase (CDC2)-Positive Cells That Were Phosphorylated (pCDC2) in Skin Cells at Baseline and 8 Hours After MK-1775 Dosing | Baseline, 8 hours after first MK-1775 dose | The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total CDC2-positive cells that were pCDC2 positive (% pCDC2-positive cells) at baseline and 8 hours after MK-1775 dosing were reported for participants in Part 1, 2-A, and 2-B/3 treatment groups with available data per protocol. |
| Primary | Percentage of Total pCDC2 in Skin Cells at Baseline and 24 Hours After MK-1775 Dosing | Baseline, 24 hours after first MK-1775 dose | The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total pCDC2 at baseline and 24 hours after MK-1775 dosing were reported for participants in the Part 2-B/3 MK-1775 QD x2 Multi Dose plus Gemcitabine treatment groups with available data per protocol. |
| Primary | Percentage of Total pCDC2 in Skin Cells at Baseline and 48 Hours After MK-1775 Dosing | Baseline, 48 hours after first MK-1775 dose | The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total pCDC2 at baseline and at 48 hours after MK-1775 dosing were reported for participants in the Part 2-B/3 MK-1775 (150 mg, 200 mg, 250) BID x 2.5 Multi Dose plus cisplatin 75 mg/m\^2 groups and the 325 mg BID x2.5 Multi Dose + Carboplatin group with available data per protocol. |
| Primary | Plasma Concentration of MK-1775 at 8 Hours After Administration (C8hr) of Single or Multiple Oral Doses | 8 hours after MK-1775 dose | MK-1775 was measured in the plasma at 8 hours after dosing (Day 1 for single dose of monotherapy, Day 2 of single-dose combination therapy and QD x 2 Combination dosing, and Day 3 dose for BID X 2.5 combination dosing) for participants with available data. |
| Primary | Mean Urine Excretion of MK-1775 24 Hours After the Day 1 Monotherapy Dose | At 0-4 hours, 4-8 hours, and 12-24 hours post Day 1 dose of monotherapy | The mean cumulative amount of MK-1775 excreted unchanged in urine after a single oral dose was measured during the initial monotherapy cycle of the study. For this outcome measure, samples were collected and analyzed only for the MK-1775 monotherapy arms of the study at defined intervals after the Day 1 dose of monotherapy. Part 2 MK-1775 combination arms were not sampled per protocol. |
| Secondary | Best Overall Response as Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | From Day 1 up through discontinuation of study treatment (up to ~11.2 months) | Best overall response achieved by a participant. Starting at Day 1, participants in Part 2 were evaluated for tumor response every 6-8 weeks until discontinuation from study treatment according to RECIST criteria; which are based on radiographic imaging. Recorded responses were either confirmed by Central Review or unconfirmed (Investigator assessment only), and included complete response (CR; defined as disappearance of all target lesions), partial response (PR; at least a 30% decrease in the sum of the longest diameter \[LD\] of target lesions, taking as reference the baseline sum LD), stable disease (SD; neither sufficient shrinkage to qualify for PR nor sufficient growth to qualify for PD, taking as reference the smallest sum LD since the treatment started), or progressive disease (PD; ≥20% increase in sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions). |
Source ClinicalTrials.gov
Outcomes7
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | Part 1: Up to 14 days, Part 2: Up to 28 days | All participants who received at least one dose of study treatment and were evaluable for DLT. | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | Percentage of Total Cyclin-dependent Kinase (CDC2)-Positive Cells That Were Phosphorylated (pCDC2) in Skin Cells at Baseline and 8 Hours After MK-1775 Dosing | Baseline, 8 hours after first MK-1775 dose | Participants in Parts 1, 2-A, and 2-B/3 with ≥1 dose treatment and evaluable CDC2 data at 8 hours post dosing. Per protocol the MK-1775 QD x2.5 Multi Dose + Gemcitabine groups, MK-1775 150, 200, and 250 mg BID x 2.5 Multi Dose + cisplatin 75 mg/m\^2 groups, and MK-1775 325 mg BID x 2.5 Multi Dose + carboplatin AUC 5 group did not have data reported | percentage of cells | GEOMETRIC_LEAST_SQUARES_MEAN |
| PRIMARY | Percentage of Total pCDC2 in Skin Cells at Baseline and 24 Hours After MK-1775 Dosing | Baseline, 24 hours after first MK-1775 dose | All participants in the Part 2-B/3 MK-1775 QD x2 Multi Dose plus Gemcitabine treatment groups who received at least one dose of study treatment and had evaluable CDC2 data at 24 hours post dosing. Per protocol, the Part 1, Part 2-A, and Part 2-B/3 MK-1775 BID treatment groups did not have data reported for this time point. | percentage of cells | GEOMETRIC_LEAST_SQUARES_MEAN |
| PRIMARY | Percentage of Total pCDC2 in Skin Cells at Baseline and 48 Hours After MK-1775 Dosing | Baseline, 48 hours after first MK-1775 dose | All participants in Part 2-B/3 MK-1775 (150 mg, 200 mg, 250) BID x 2.5 Multi Dose plus cisplatin 75 mg/m\^2 groups and 325 mg BID x2.5 Multi Dose + carboplatin group who received ≥1 dose of study treatment and had evaluable CDC2 data at 48 hours post dose. Per protocol, Part 1, Part 2-A, and remaining Part 2-B/3 groups did not have data reported. | percentage of cells | GEOMETRIC_LEAST_SQUARES_MEAN |
| PRIMARY | Plasma Concentration of MK-1775 at 8 Hours After Administration (C8hr) of Single or Multiple Oral Doses | 8 hours after MK-1775 dose | All treated participants with available C8hr data. | nM | MEAN |
| PRIMARY | Mean Urine Excretion of MK-1775 24 Hours After the Day 1 Monotherapy Dose | At 0-4 hours, 4-8 hours, and 12-24 hours post Day 1 dose of monotherapy | All treated Part 1 participants with available urine sample data. | mg | MEAN |
| SECONDARY | Best Overall Response as Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | From Day 1 up through discontinuation of study treatment (up to ~11.2 months) | All treated participants in Part 2 with measurable disease at baseline per RECIST criteria. Participants who were originally treated in Part 1 and continued in Part 2 were included in their respective Part 2 arms. Participants who could not be evaluated after treatment are categorized as not evaluable (NE). | Participants | COUNT_OF_PARTICIPANTS |
Source ClinicalTrials.gov
Results by group281
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | MK-1775 325 mg Single Dose | 0 | Participants | ||
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | MK-1775 650 mg Single Dose | 0 | Participants | ||
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | MK-1775 1300 mg Single Dose | 0 | Participants | ||
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 | 0 | Participants | ||
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 | 2 | Participants | ||
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 | 0 | Participants | ||
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 | 2 | Participants | ||
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | 0 | Participants | ||
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | 0 | Participants | ||
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | 0 | Participants |
1 to 10 of 281Source ClinicalTrials.gov
See all 281 results by groupParticipant flow112
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | MK-1775 325 mg Single Dose | 3 | |
| Overall Study | STARTED | MK-1775 650 mg Single Dose | 3 | |
| Overall Study | STARTED | MK-1775 1300 mg Single Dose | 3 | |
| Overall Study | STARTED | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2 | 4 | |
| Overall Study | STARTED | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2 | 9 | |
| Overall Study | STARTED | MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2 | 1 | |
| Overall Study | STARTED | MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2 | 10 | |
| Overall Study | STARTED | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | 1 | |
| Overall Study | STARTED | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | 3 | |
| Overall Study | STARTED | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | 10 |
1 to 10 of 112Source ClinicalTrials.gov
See all 112 participant flowAdverse events10,752
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MK-1775 325 mg Single Dose | 1 | 3 | 2 |
| other | Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MK-1775 650 mg Single Dose | 0 | 3 | |
| other | Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MK-1775 1300 mg Single Dose | 0 | 3 | |
| other | Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m2 | 0 | 6 | |
| other | Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m2 | 0 | 8 | |
| other | Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MK-1775 100 mg Single Dose + Cisplatin 75 mg/m2 | 0 | 3 | |
| other | Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MK-1775 200 mg Single Dose + Cisplatin 75 mg/m2 | 0 | 10 | |
| other | Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | 0 | 3 | |
| other | Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | 0 | 4 | |
| other | Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | 0 | 9 |
1 to 10 of 10,752Source ClinicalTrials.gov
See all 10,752 adverse eventsAdverse event totals84
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | MK-1775 325 mg Single Dose | 0 | 3 |
| Total, all-cause mortality | MK-1775 650 mg Single Dose | 0 | 3 |
| Total, all-cause mortality | MK-1775 1300 mg Single Dose | 0 | 3 |
| Total, all-cause mortality | MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m2 | 0 | 6 |
| Total, all-cause mortality | MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m2 | 1 | 8 |
| Total, all-cause mortality | MK-1775 100 mg Single Dose + Cisplatin 75 mg/m2 | 0 | 3 |
| Total, all-cause mortality | MK-1775 200 mg Single Dose + Cisplatin 75 mg/m2 | 0 | 10 |
| Total, all-cause mortality | MK-1775 100 mg Single Dose + Carboplatin AUC 5 | 0 | 3 |
| Total, all-cause mortality | MK-1775 200 mg Single Dose + Carboplatin AUC 5 | 0 | 4 |
| Total, all-cause mortality | MK-1775 325 mg Single Dose + Carboplatin AUC 5 | 0 | 9 |
1 to 10 of 84Source ClinicalTrials.gov
See all 84 adverse event totalsPapers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 27601554 | DERIVED |
Source PubMed
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
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