Trial · NCT03387020
Ribociclib and Everolimus in Treating Children With Recurrent or Refractory Malignant Brain Tumors
NCT03387020, Phase 1, Completed, Pediatric Brain Tumor Consortium; results first posted 2021-08-27
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Ribociclib and Everolimus in Treating Children With Recurrent or Refractory Malignant Brain Tumors. Trials, record NCT03387020. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03387020
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Ribociclib and Everolimus in Treating Children With Recurrent or Refractory Malignant Brain Tumors
- NCT number
- NCT03387020
- Status
- Completed
- Phases
- Phase 1
- Enrollment
- 22 participants, actual
- Lead sponsor
- Pediatric Brain Tumor Consortium
- Conditions
CNS Embryonal Tumor, Not Otherwise Specified, Malignant Glioma, Recurrent Atypical Teratoid/Rhabdoid Tumor, Recurrent Childhood Ependymoma, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Medulloblastoma, Refractory Diffuse Intrinsic Pontine Glioma
- Interventions
- Everolimus, Laboratory Biomarker Analysis, Pharmacological Study, Ribociclib
- First posted
- 2017-12-29
- Last updated
- 2021-08-27
- Results first posted
- 2021-08-27
Source ClinicalTrials.gov
Registered outcomes8
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Maximum Tolerated Dose of Ribociclib and Everolimus | 4 weeks | Defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic. Will be estimated using a Rolling-6 phase I design. Only patients who are evaluable for DLT will be consider for estimating of Maximum Tolerated Dose. Patient who were enrolled under Surgical cohort but received sufficient study defined treatment would also be evaluable for DLT. |
| Primary | Average Tumor and Plasma Concentrations of Ribociclib for the Surgical Study | Surgical study: Prior to starting ribociclib (day -7 or -10), prior to ribociclib dose on days -5 & -2, day 0, and at the time of surgery | Average tumor Ribociclib concentrations will be compared to plasma concentrations. The mean tumor-to-plasma ratio of Ribociclib at the time of surgery will be described. |
| Secondary | Objective Responses (Complete Response + Partial Response) | Up to 2 years | Number of patients with sustained objective responses will be reported by stratum and dose. Objective response refers to at least 50% reduction in 2 dimensional measurements of the tumor. In order to count towards this objective, any response needs to be sustained for at least 8 weeks. |
| Secondary | Percent Change in ki67 Between Archival and Post-treatment Tissue | Up to 2 years | For the surgical study, Ki67 will be evaluated in paired pre-treatment tumor (diagnostic) and post-treatment tumor (recurrent) tissue in consenting patients to assess percent change. The percent of Ki67 in tumor tissues will be measured and the result is presented as the percent of Ki67 in post-treatment tumor minus the percent of Ki67 measured in pre-treatment tumor. |
| Other | Ribociclib AUC (Area Under the Plasma Concentration Versus Time Curve) as Obtained From the Patients Who Received Phase I Defined Treatment | Pre-dose, 1, 2, 4, 8, 24, 32 (day 1 course 1 only), & 48 (day 1 course 1 only) hours after dose on days 1 and 17 of course 1. | Ribociclib plasma concentration-time data obtained from patients who received Phase I defined treatment will be modeled using compartmental approaches to estimate the AUC (hr\*μM) for each dose level on days 1 and 17 of course 1. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment. |
| Other | Everolimus AUC (Area Under the Plasma Concentration Versus Time Curve) as Obtained From the Phase I Study | Pre-dose, 0.5 (course 2 only), 1, 1.5 (course 2 only), 2, 4, 6 (course 2 only), 8, 24 hours after dose on day 17 of course 1, and day 1 of course 2. | Everolimus plasma concentration-time data obtained from patients who received Phase I defined treatment will be modeled using compartmental approaches to estimate the AUC (hr\*nM) for each dose level on day 17 of course 1 and day 1 of course 2. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment. |
| Other | Ribociclib Half-Life as Obtained From the Phase 1 Study | Pre-dose, 1, 2, 4, 8, 24, 32 (day 1 course 1 only), & 48 (day 1 course 1 only) hours after dose on days 1 and 17 of course 1. | Ribociclib plasma concentration-time data obtained from patients received Phase I defined treatment will be modeled using compartmental approaches to estimate the half-life (hrs) for each dose level on days 1 and 17 of course 1. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment. |
| Other | Everolimus Half Life as Obtained From the Phase 1 Study | Pre-dose, 0.5 (course 2 only), 1, 1.5 (course 2 only), 2, 4, 6 (course 2 only), 8, & 24 hours after dose on day 17 of course 1, and day 1 of course 2 | Everolimus plasma concentration-time data obtained from patients received Phase I defined treatment will be modeled using compartmental approaches to estimate the half-life (hrs) for each dose level on day 17 of course 1 and day 1 of course 2. Patients who were enrolled in the Surgical stratum but subsequently received Phase I defined treatment with PK data available will also be included in the analysis population. 5 patients from surgical stratum received dose level 1 treatment. |
Source ClinicalTrials.gov
Outcomes8
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Maximum Tolerated Dose of Ribociclib and Everolimus | 4 weeks | Patients who were evaluable for dose finding assessment were used to determine the MTD. Evaluable patients are those who were eligible, started treatment and either experienced a dose limiting toxicity during course 1 or received adequate amount of treatment and were followed adequately to be assessed for safety during course 1. Evaluable patients could be from either Phase I stratum or from Surgical stratum as long as they received sufficient protocol defined Phase I treatment. | mg/m^2/day | NUMBER |
| PRIMARY | Average Tumor and Plasma Concentrations of Ribociclib for the Surgical Study | Surgical study: Prior to starting ribociclib (day -7 or -10), prior to ribociclib dose on days -5 & -2, day 0, and at the time of surgery | Patients who were enrolled on surgical study and with tumor and matching plasma samples available. | ratio | MEDIAN |
| SECONDARY | Objective Responses (Complete Response + Partial Response) | Up to 2 years | Patients who received Phase I treatment were included in the analysis. One patient in Phase I study withdrew prior to beginning protocol therapy and one patient in Surgical study was not eligible to start Phase I treatment. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Percent Change in ki67 Between Archival and Post-treatment Tissue | Up to 2 years | Consented patients in surgical study with pre-treatment tumor and post-treatment tumor tissue available | Change of Percentage of Ki67 in Tumor | MEDIAN |
| OTHER_PRE_SPECIFIED | Ribociclib AUC (Area Under the Plasma Concentration Versus Time Curve) as Obtained From the Patients Who Received Phase I Defined Treatment | Pre-dose, 1, 2, 4, 8, 24, 32 (day 1 course 1 only), & 48 (day 1 course 1 only) hours after dose on days 1 and 17 of course 1. | Patients with blood samples collected for pharmacokinetic studies on days 1 and 17 of course 1 were included. Surgical patients who received Phase I treatment with samples collected were also included in Dose Level 1. There are total 17 patients received dose level 1 treatment and 3 patients received dose level 2 treatment. | hr*uM | MEDIAN |
| OTHER_PRE_SPECIFIED | Everolimus AUC (Area Under the Plasma Concentration Versus Time Curve) as Obtained From the Phase I Study | Pre-dose, 0.5 (course 2 only), 1, 1.5 (course 2 only), 2, 4, 6 (course 2 only), 8, 24 hours after dose on day 17 of course 1, and day 1 of course 2. | Patients with blood samples collected for pharmacokinetic studies on day 17 of course 1 and day 1 of course 2 were included. Surgical patients who received Phase I treatment with samples collected were also included in Dose Level 1. There are total 17 patients received dose level 1 treatment and 3 patients received dose level 2 treatment. Analysis population only includes treated patients with corresponding PK data available. | hr*nM | MEDIAN |
| OTHER_PRE_SPECIFIED | Ribociclib Half-Life as Obtained From the Phase 1 Study | Pre-dose, 1, 2, 4, 8, 24, 32 (day 1 course 1 only), & 48 (day 1 course 1 only) hours after dose on days 1 and 17 of course 1. | Patients with blood samples collected for pharmacokinetic studies on days 1 and 17 of course 1 were included. Surgical patients who received Phase I treatment with samples collected were also included in Dose Level 1. There are total 17 patients received dose level 1 treatment and 3 patients received dose level 2 treatment. The analysis population only includes patients with corresponding PK data available at that timepoint. | hours | MEDIAN |
| OTHER_PRE_SPECIFIED | Everolimus Half Life as Obtained From the Phase 1 Study | Pre-dose, 0.5 (course 2 only), 1, 1.5 (course 2 only), 2, 4, 6 (course 2 only), 8, & 24 hours after dose on day 17 of course 1, and day 1 of course 2 | Patients with blood samples collected for pharmacokinetic studies on day 17 of course 1 and day 1 of course 2 were included. Surgical patients who received Phase I treatment with samples collected were also included in Dose Level 1. There are total 17 patients received dose level 1 treatment and 3 patients received dose level 2 treatment. The analysis population only includes patients with corresponding PK data available at that timepoint. | hours | MEDIAN |
Source ClinicalTrials.gov
Results by group23
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Maximum Tolerated Dose of Ribociclib and Everolimus | DLT Evaluable Set | Ribociclib | 120 | mg/m^2/day | |
| Maximum Tolerated Dose of Ribociclib and Everolimus | DLT Evaluable Set | Everolumus | 1.2 | mg/m^2/day | |
| Average Tumor and Plasma Concentrations of Ribociclib for the Surgical Study | Surgical | 14.6 | Full Range 2.22 to 53.4 | ratio | |
| Objective Responses (Complete Response + Partial Response) | Phase I, Dose Level 1 | 0 | Participants | ||
| Objective Responses (Complete Response + Partial Response) | Phase I, Dose Level 2 | 0 | Participants | ||
| Objective Responses (Complete Response + Partial Response) | Surgical | 0 | Participants | ||
| Percent Change in ki67 Between Archival and Post-treatment Tissue | Surgical | -20 | Full Range -35 to -5 | Change of Percentage of Ki67 in Tumor | |
| Ribociclib AUC (Area Under the Plasma Concentration Versus Time Curve) as Obtained From the Patients Who Received Phase I Defined Treatment | Dose Level 1, Day 1 of Course 1 | 3.96 | Full Range 2.6 to 11.2 | hr*uM | |
| Ribociclib AUC (Area Under the Plasma Concentration Versus Time Curve) as Obtained From the Patients Who Received Phase I Defined Treatment | Dose Level 1, Day 17 of Course 1 | 10.3 | Full Range 5.3 to 18.7 | hr*uM | |
| Ribociclib AUC (Area Under the Plasma Concentration Versus Time Curve) as Obtained From the Patients Who Received Phase I Defined Treatment | Dose Level 2, Day 1 of Course 1 | 12.0 | Full Range 5.4 to 13.4 | hr*uM |
1 to 10 of 23Source ClinicalTrials.gov
See all 23 results by groupParticipant flow12
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Phase I, Dose Level 1 | 13 | |
| Overall Study | STARTED | Phase I, Dose Level 2 | 3 | |
| Overall Study | STARTED | Surgical | 5 | |
| Overall Study | Received Treatment | Phase I, Dose Level 1 | 12 | |
| Overall Study | Received Treatment | Phase I, Dose Level 2 | 3 | |
| Overall Study | Received Treatment | Surgical | 5 | |
| Overall Study | COMPLETED | Phase I, Dose Level 1 | 11 | |
| Overall Study | COMPLETED | Phase I, Dose Level 2 | 1 | |
| Overall Study | COMPLETED | Surgical | 5 | |
| Overall Study | NOT COMPLETED | Phase I, Dose Level 1 | 2 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 participant flowAdverse events162
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 | Anemia | Blood and lymphatic system disorders | Phase I, Dose Level 1 | 4 | 12 | 6 |
| other | Anemia | Blood and lymphatic system disorders | Phase I, Dose Level 2 | 1 | 3 | 11 |
| other | Anemia | Blood and lymphatic system disorders | Surgical | 4 | 5 | 8 |
| other | Corneal ulcer | Eye disorders | Phase I, Dose Level 1 | 0 | 12 | 0 |
| other | Corneal ulcer | Eye disorders | Phase I, Dose Level 2 | 1 | 3 | 1 |
| other | Corneal ulcer | Eye disorders | Surgical | 0 | 5 | 0 |
| other | Abdominal pain | Gastrointestinal disorders | Phase I, Dose Level 1 | 1 | 12 | 1 |
| other | Abdominal pain | Gastrointestinal disorders | Phase I, Dose Level 2 | 0 | 3 | 0 |
| other | Abdominal pain | Gastrointestinal disorders | Surgical | 1 | 5 | 1 |
| other | Diarrhea | Gastrointestinal disorders | Phase I, Dose Level 1 | 0 | 12 | 0 |
1 to 10 of 162Source ClinicalTrials.gov
See all 162 adverse eventsAdverse event totals9
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Phase I, Dose Level 1 | 5 | 12 |
| Total, all-cause mortality | Phase I, Dose Level 2 | 0 | 3 |
| Total, all-cause mortality | Surgical | 0 | 5 |
| Total, other adverse events | Phase I, Dose Level 1 | 12 | 12 |
| Total, other adverse events | Phase I, Dose Level 2 | 3 | 3 |
| Total, other adverse events | Surgical | 5 | 5 |
| Total, serious adverse events | Phase I, Dose Level 1 | 6 | 12 |
| Total, serious adverse events | Phase I, Dose Level 2 | 1 | 3 |
| Total, serious adverse events | Surgical | 1 | 5 |
Source ClinicalTrials.gov
Papers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants1
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.
| Project | Title | Principal investigators | Organization | Funder | Fiscal years |
|---|---|---|---|---|---|
| UM1CA081457 | Pediatric Brain Tumor Consortium A multi-institutional consortium devoted to novel phase I and II clinical evaluations of experimental treatment approaches for pediatric CNS tumors | ONAR-THOMAS, ARZU; DUNKEL, IRA J | ST. JUDE CHILDREN'S RESEARCH HOSPITAL | NATIONAL CANCER INSTITUTE | 2014 to 2025 |
Source NIH RePORTER
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.
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