Trial · NCT01877382
A Multiple Ascending Dose Study of Milademetan in Subjects With Advanced Solid Tumors or Lymphomas
NCT01877382, Phase 1, Completed, Daiichi Sankyo; results first posted 2024-07-18
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Multiple Ascending Dose Study of Milademetan in Subjects With Advanced Solid Tumors or Lymphomas. Trials, record NCT01877382. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01877382
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Multiple Ascending Dose Study of Milademetan in Subjects With Advanced Solid Tumors or Lymphomas
- NCT number
- NCT01877382
- Status
- Completed
- Phases
- Phase 1
- Enrollment
- 107 participants, actual
- Lead sponsor
- Daiichi Sankyo
- Conditions
- Advanced Solid Tumor, Lymphoma
- Interventions
- Milademetan, Milademetan
- First posted
- 2013-06-13
- Last updated
- 2025-03-27
- Results first posted
- 2024-07-18
Source ClinicalTrials.gov
Registered outcomes9
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Screening until end of treatment visit, up to approximately 7 years 2 months | A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerged during the treatment period (from first dose date until 30 days after the last dosing date), having been absent at pretreatment; or reemerged during treatment, having been present at baseline, but stopped prior to treatment; or worsened in severity after starting treatment relative to the pretreatment state, when the AE was continuous. |
| Primary | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Cycle 1, Day 1 to Day 28 (each cycle, 28 days) | A dose-limiting toxicity (DLT) was defined as any treatment-emergent AE (TEAE) not attributable to the participant's disease or a disease-related processes that occurred during the observation period (Cycle 1) in each dose-level cohort and was Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0, with a few exceptions. |
| Primary | Number of Participants With Melanoma and Diffuse Large B Cell Lymphoma Who Achieved Objective Response | Screening up to Cycle 3 and beyond, Day 1 (each cycle, 28 days) | Tumor response was assessed using RECIST Version 1.1 (in solid tumor participants with measurable disease) or treatment response using the revised International Working Group criteria 7 (in participants with lymphoma). For RECIST, complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Objective response rate (ORR) was the sum of CR and PR rates. |
| Secondary | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods. |
| Secondary | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Area under the curve from time 0 to 24 hours (AUC0-24), time 0 to infinity (AUCinf), and to the last measurable concentration (AUClast). Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods. |
| Secondary | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods. |
| Secondary | Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods. |
| Secondary | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Plasma pharmacokinetic parameters of DS-3032a were calculated using noncompartmental methods. |
| Secondary | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 and Cycle 1, Days 18 to 21 (each cycle is 28 days) | Mean fold change in macrophage inhibitory cytokine-1 (MIC-1) levels in serum from baseline are summarized using descriptive statistics by cohort. |
Source ClinicalTrials.gov
Outcomes9
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Screening until end of treatment visit, up to approximately 7 years 2 months | Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set. | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | Number of Participants With Dose-Limiting Toxicities In Participants Receiving Milademetan by Preferred Term and Worst Grade by NCI CTCAE | Cycle 1, Day 1 to Day 28 (each cycle, 28 days) | Dose-limiting toxicities were assessed in the DLT Evaluable Set in cohorts with available patient data. DLTs were not evaluated in the Expansion Cohort. | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | Number of Participants With Melanoma and Diffuse Large B Cell Lymphoma Who Achieved Objective Response | Screening up to Cycle 3 and beyond, Day 1 (each cycle, 28 days) | Objective response was assessed in the Dose Expansion cohort of the Full Analysis Set. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | ng/mL | MEAN |
| SECONDARY | Pharmacokinetic Parameter Area Under the Curve (AUC) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Pharmacokinetic parameters were assessed in participants with available data in the Pharmacokinetic Analysis Set. | ng*h/mL | MEAN |
| SECONDARY | Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (Tmax) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Pharmacokinetic parameters were assessed in participants with available data in the Pharmacokinetic Analysis Set. | hours | MEDIAN |
| SECONDARY | Pharmacokinetic Parameter Apparent Clearance (CL/F) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Pharmacokinetic parameters were assessed in participants with available data in the Pharmacokinetic Analysis Set. | L/h | MEDIAN |
| SECONDARY | Pharmacokinetic Parameter Elimination Terminal Half Life Half-Life (T1/2) of Milademetan In Participants Receiving Milademetan | Escalation:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,6-8 hours(h);Cycle 2,Day 1 Predose,1,3,6-8h,30 days after last dose; Expansion:Cycle 1,Days 1,2,8,15,18-21 Predose,0.5,1,2,3,4,6,8h;Cycle 2,Day 1 Predose,1,2,3,4,6,8h and Day 2 (each cycle, 28 days) | Pharmacokinetic parameters were assessed in participants with available data in the Pharmacokinetic Analysis Set. | hours | MEAN |
| SECONDARY | Mean Fold Change From Baseline in Serum MIC-1 Levels in Participants Receiving Milademetan | Cycle 1, Day 15 and Cycle 1, Days 18 to 21 (each cycle is 28 days) | Serum MIC-1 levels were assessed in the Biomarker Analysis Set in participants with available data. | fold change | MEAN |
Source ClinicalTrials.gov
Results by group701
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cohort 1: 15 mg/Day Milademetan | Any TEAE | 3 | Participants | |
| Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cohort 2: 30 mg/Day Milademetan | Any TEAE | 1 | Participants | |
| Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cohort 3: 60 mg/Day Milademetan | Any TEAE | 1 | Participants | |
| Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | Any TEAE | 33 | Participants | |
| Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cohort 5: 240 mg/Day Milademetan | Any TEAE | 2 | Participants | |
| Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cohort 6: 160 mg/Day Milademetan | Any TEAE | 5 | Participants | |
| Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cohort 7b: 90 mg/Day Milademetan | Any TEAE | 9 | Participants | |
| Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cohort 8c: 90 mg/Day Milademetan | Any TEAE | 15 | Participants | |
| Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cohort 9d: 120 mg/Day Milademetan | Any TEAE | 6 | Participants | |
| Number of Participants With Treatment-emergent Adverse Events (≥10% Overall) in Participants Receiving Milademetan | Cohort 10e: 120 mg/Day Milademetan | Any TEAE | 3 | Participants |
1 to 10 of 701Source ClinicalTrials.gov
See all 701 results by groupParticipant flow90
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Dose Escalation | STARTED | Cohort 1: 15 mg/Day Milademetan | 3 | |
| Dose Escalation | STARTED | Cohort 2: 30 mg/Day Milademetan | 1 | |
| Dose Escalation | STARTED | Cohort 3: 60 mg/Day Milademetan | 1 | |
| Dose Escalation | STARTED | Cohort 4: 120 mg/Day Milademetan | 13 | |
| Dose Escalation | STARTED | Cohort 5: 240 mg/Day Milademetan | 2 | |
| Dose Escalation | STARTED | Cohort 6: 160 mg/Day Milademetan | 5 | |
| Dose Escalation | STARTED | Cohort 7b: 90 mg/Day Milademetan | 9 | |
| Dose Escalation | STARTED | Cohort 8c: 90 mg/Day Milademetan | 15 | |
| Dose Escalation | STARTED | Cohort 9d: 120 mg/Day Milademetan | 6 | |
| Dose Escalation | STARTED | Cohort 10e: 120 mg/Day Milademetan | 3 |
1 to 10 of 90Source ClinicalTrials.gov
See all 90 participant flowAdverse events3,108
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 | Nausea | Gastrointestinal disorders | Cohort 1: 15 mg/Day Milademetan | 1 | 3 | |
| other | Nausea | Gastrointestinal disorders | Cohort 2: 30 mg/Day Milademetan | 0 | 1 | |
| other | Nausea | Gastrointestinal disorders | Cohort 3: 60 mg/Day Milademetan | 0 | 1 | |
| other | Nausea | Gastrointestinal disorders | Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | 22 | 33 | |
| other | Nausea | Gastrointestinal disorders | Cohort 5: 240 mg/Day Milademetan | 2 | 2 | |
| other | Nausea | Gastrointestinal disorders | Cohort 6: 160 mg/Day Milademetan | 5 | 5 | |
| other | Nausea | Gastrointestinal disorders | Cohort 7b: 90 mg/Day Milademetan | 7 | 9 | |
| other | Nausea | Gastrointestinal disorders | Cohort 8c: 90 mg/Day Milademetan | 13 | 15 | |
| other | Nausea | Gastrointestinal disorders | Cohort 9d: 120 mg/Day Milademetan | 4 | 6 | |
| other | Nausea | Gastrointestinal disorders | Cohort 10e: 120 mg/Day Milademetan | 1 | 3 |
1 to 10 of 3,108Source ClinicalTrials.gov
See all 3,108 adverse eventsAdverse event totals42
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Cohort 1: 15 mg/Day Milademetan | 0 | 3 |
| Total, all-cause mortality | Cohort 2: 30 mg/Day Milademetan | 0 | 1 |
| Total, all-cause mortality | Cohort 3: 60 mg/Day Milademetan | 0 | 1 |
| Total, all-cause mortality | Cohort 4: 120 mg/Day Milademetan + Expansion Cohort | 3 | 33 |
| Total, all-cause mortality | Cohort 5: 240 mg/Day Milademetan | 0 | 2 |
| Total, all-cause mortality | Cohort 6: 160 mg/Day Milademetan | 0 | 5 |
| Total, all-cause mortality | Cohort 7b: 90 mg/Day Milademetan | 0 | 9 |
| Total, all-cause mortality | Cohort 8c: 90 mg/Day Milademetan | 1 | 15 |
| Total, all-cause mortality | Cohort 9d: 120 mg/Day Milademetan | 0 | 6 |
| Total, all-cause mortality | Cohort 10e: 120 mg/Day Milademetan | 0 | 3 |
1 to 10 of 42Source ClinicalTrials.gov
See all 42 adverse event totalsPapers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 36669146 | RESULT |
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
Read this trial from software.
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