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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Given PO
Children's Hospital of Alabama
Birmingham, Alabama, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Banner Children's at Desert
Mesa, Arizona, United States
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Banner University Medical Center - Tucson
Tucson, Arizona, United States
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
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Arkansas Children's Hospital
Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center
Downey, California, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Loma Linda University Medical Center
Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States
...and 164 more locations