A Phase 2 interventional study of Ivosidenib in Recurrent Ependymoma, Recurrent Ewing Sarcoma and Recurrent Hepatoblastoma, sponsored by National Cancer Institute (NCI). Active, not recruiting at 174 sites in 3 countries. Open to participants aged 12 Months to 21 Years. Per ClinicalTrials.gov, last updated 2026-07-01.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
This phase II Pediatric MATCH trial studies how well ivosidenib works in treating patients with solid tumors, including central nervous system tumors, lymphomas and histiocytic disorders that have not responded to (refractory) or have come back after (recurrent) prior treatment that have IDH (isocitrate dehydrogenase) 1 genetic alterations (mutations). Ivosidenib may block the growth of cancer cells that have specific genetic changes in an important signaling pathway called the IDH pathway.
PRIMARY OBJECTIVE:
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with AG-120 (ivosidenib) with advanced solid tumors (including central nervous system [CNS] tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in the IDH1 pathway.
SECONDARY OBJECTIVES:
I. To estimate the progression free survival in pediatric patients treated with AG-120 (ivosidenib) with advanced solid tumors (including CNS tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in the IDH1 pathway.
II. To obtain information about the tolerability of AG-120 (ivosidenib) in children and adolescents with relapsed or refractory cancer.
III. To provide preliminary estimates of the pharmacokinetics and pharmacodynamics of AG-120 (ivosidenib) in children and adolescents with relapsed or refractory cancer.
EXPLORATORY OBJECTIVES:
I. To evaluate other biomarkers as predictors of response to AG-120 (ivosidenib) and specifically, whether tumors that harbor different missense mutations or fusions will demonstrate differential response to AG-120 (ivosidenib) treatment.
II. To explore approaches to the profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
OUTLINE:
Patients receive ivosidenib orally (PO) once daily (QD). Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG)+ evaluable disease are eligible. Measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
Note: The following do not qualify as measurable disease:
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
Stem cell infusions (with or without total body irradiation [TBI]):
Radiation therapy (XRT)/external beam Irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
A serum creatinine based on age/gender (within 7 days prior to enrollment)
Corrected QT (QTc )interval =\< 450 milliseconds (within 7 days prior to enrollment)
Exclusion Criteria:
Patients receive ivosidenib PO QD. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Drug: Ivosidenib
Given PO
Also known as: AG 120, AG-120, AG120, Tibsovo
Objective Response Rate (ORR; Complete Response + Partial Response) in Pediatric Patients Treated With Ivosidenib
A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders. The revised Response Evaluation Criteria in Solid Tumors guideline (version 1.1) was used to determine response and progression in this study, with specific criteria outlined for the different subtypes of tumors (e.g., 2-dimensional measurements for central nervous system tumors).
Time frame: Up to 2 years from study entry
Progression Free Survival (PFS)
The Kaplan-Meier method will be used to estimate the 6 month PFS. PFS is defined as time from initiation of protocol treatment to disease progression, recurrence, death from any cause, or date of last contact.
Time frame: Up to 6 months from study entry
Percentage of Patients Experiencing Grade 3 or Higher Adverse Events
Percentage of patients experiencing grade 3 or higher adverse events will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Time frame: Up to 2 years from study entry
Preliminary Estimates of the Pharmacokinetics (PK) of Ivosidenib in Children and Adolescents With Relapsed or Refractory Cancer
A descriptive analysis of PK parameters will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
Time frame: Pre-dose, 1, 2, 3, 4, and 6-8 hours after dose on cycle 1, day 1; pre-dose on cycle 1, day 2; pre-dose, 1, 2, 3, 4, and 6-8 hours after dose on cycle 1, day 15; and pre-dose on cycle 2, day 1 and cycle 4, day 1
Preliminary Estimates of the Pharmacodynamics (PD) of Ivosidenib in Children and Adolescents With Relapsed or Refractory Cancer
Time frame: Pre-dose, 1, 2, 3, 4, and 6-8 hours after dose on cycle 1, day 1; pre-dose on cycle 1, day 2; pre-dose, 1, 2, 3, 4, and 6-8 hours after dose on cycle 1, day 15; and pre-dose on cycle 2, day 1 and cycle 4, day 1
Biomarker Analysis
Will evaluate other biomarkers as predictors of response to ivosidenib and whether tumors that harbor different missense mutations or fusions will demonstrate differential response to treatment. A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
Time frame: Up to 5 years
Profiling Changes in Tumor Genomics
Will explore approaches to the profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid. A descriptive analysis will be performed and will be summarized with simple summary statistics.
Time frame: Baseline up to 5 years
| Milestone | Treatment (Ivosidenib) |
|---|---|
| Started | 3 |
| Completed | 0 |
| Not completed | 3 |
| Withdrew: Progressive disease | 1 |
| Withdrew: Refusal by patient/parent/guardian | 1 |
| Withdrew: No treatment | 1 |
A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders. The revised Response Evaluation Criteria in Solid Tumors guideline (version 1.1) was used to determine response and progression in this study, with specific criteria outlined for the different subtypes of tumors (e.g., 2-dimensional measurements for central nervous system tumors).
| percentage of participants | Treatment (Ivosidenib) |
|---|---|
| Objective Response Rate (ORR; Complete Response + Partial Response) in Pediatric Patients Treated With Ivosidenib | 0 (0 to 0) |
The Kaplan-Meier method will be used to estimate the 6 month PFS. PFS is defined as time from initiation of protocol treatment to disease progression, recurrence, death from any cause, or date of last contact.
Results for this outcome have not been posted.
Percentage of patients experiencing grade 3 or higher adverse events will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Results for this outcome have not been posted.
A descriptive analysis of PK parameters will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
Results for this outcome have not been posted.
Results for this outcome have not been posted.
Will evaluate other biomarkers as predictors of response to ivosidenib and whether tumors that harbor different missense mutations or fusions will demonstrate differential response to treatment. A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
Results for this outcome have not been posted.
Will explore approaches to the profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid. A descriptive analysis will be performed and will be summarized with simple summary statistics.
Results for this outcome have not been posted.
Collected over Adverse Events monitored/assessed from enrollment to 30 days after the end of treatment, up to 2 years. All-Cause Mortality monitored/assessed up to 5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Ivosidenib) | 1/3 (33.3%) | 1/2 (50%) | 2/2 (100%) |
| Event | Treatment (Ivosidenib) |
|---|---|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specifyNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/2 |
| Event | Treatment (Ivosidenib) |
|---|---|
| NauseaGastrointestinal disorders | 1/2 |
| VomitingGastrointestinal disorders | 1/2 |
| FatigueGeneral disorders | 1/2 |
| Blood bicarbonate decreasedInvestigations | 1/2 |
| Lymphocyte count decreasedInvestigations | 1/2 |
| Neutrophil count decreasedInvestigations | 1/2 |
| White blood cell decreasedInvestigations | 1/2 |
| HyperphosphatemiaMetabolism and nutrition disorders | 1/2 |
| HeadacheNervous system disorders | 1/2 |
| SeizureNervous system disorders | 1/2 |
| Age, Categorical(Participants) | Treatment (Ivosidenib) |
|---|---|
| <=18 years | 2 |
| Between 18 and 65 years | 1 |
| >=65 years | 0 |
| Age, Continuous(years) | Treatment (Ivosidenib) |
|---|---|
| Mean | 16.7 ± 2.5 |
| Sex: Female, Male(Participants) | Treatment (Ivosidenib) |
|---|---|
| Female | 1 |
| Male | 2 |
| Ethnicity (NIH/OMB)(Participants) | Treatment (Ivosidenib) |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 3 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Treatment (Ivosidenib) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 2 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Treatment (Ivosidenib) |
|---|---|
| United States | 3 |
Showing the first 100 of 174 sites across 3 countries.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
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