A Phase 1/2, Single-arm Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of Avapritinib in Pediatric Patients with Solid Tumors Dependent on KIT or PDGFRA Signaling

Blueprint Medicines Corporation0 sites37 target enrollmentOctober 21, 2021

ConditionsSolid Tumors Dependent on KIT or PDGFRA Signaling Therapeutic area: Diseases [C] - Cancer [C04]

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Solid Tumors Dependent on KIT or PDGFRA Signaling
Sponsor: Blueprint Medicines Corporation
Enrollment: 37
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

October 21, 2021

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Blueprint Medicines Corporation

Eligibility Criteria

Inclusion Criteria

•\- Patient is 2 to \<18 years of age at the time the parent/guardian signs the Informed Consent Form.
•\- Confirmed diagnosis of R/R solid tumor, including CNS tumor, with a mutation (including nonsynonymous point mutations, insertions, and deletions) in PDGFRA and/or KIT that has progressed despite standard therapy and no alternative treatment options are available. Patient with R/R solid tumors with only PDGFRA and/or KIT amplifications may be included with approval from the Sponsor OR
•Confirmed diagnosis of DMG\-H3K27a that has failed standard therapy or for which no standard therapy that may convey clinical benefit exists, as judged by the Investigator.
•\- Disease extent:
•\-Part 1: All patients must have at least 1 measurable lesion as defined by RECIST v1\.1 or RANO (for CNS tumors). If radiation therapy has been administered, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be \= 12 weeks from radiation to any target lesion.
•\-Part 2: All patients must have at least 1 measurable lesion as defined by RECIST v1\.1 or RANO (for CNS tumors). For patients with DMG\-H3K27a or PDGFRA and/or KIT mutant/amplified solid tumors, including CNS tumors, that have progressed despite prior therapy who have received radiation therapy, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be \= 12 weeks from radiation to any target lesion. For up to 5 patients with newly diagnosed DMG\-H3K27a where there is no standard therapy that may convey clinical benefit exists as judged by the investigator, progression of disease of a measurable lesion after irradiation is not required.
•\- Patients with CNS disease should be on a stable dose of corticosteroids for at least 7 days prior to first dose of avapritinib, with no plans for dose escalation.
•\- Patients must have a Lansky (\<16 years of age) or Karnofsky (\=16 years of age) score of at least 50\.
•Are the trial subjects under 18? yes
•Number of subjects for this age range: 37

Exclusion Criteria

•1\. Patient has any of the following within 14 days before the first dose of study treatment:
•a. Platelet count \<75 × 10\*9/L (\<100 × 10\*9/L if a CNS tumor) with no platelet transfusion within 14 days prior to the measurement.
•b. Absolute neutrophil count (ANC) \<1\.0 × 10\*9/L.
•c. Hemoglobin \<8\.0 g/dL with no RBC transfusion \=7 days prior to the measurement.
•d. AST or ALT \>3 × the ULN for age; except in patients with tumor involvement of the liver who must not have AST and ALT \>5 × ULN for age.
•e. Total bilirubin xULN for age; and in presence of Gilbert’s syndrome, total bilirubin \>3 × ULN or direct bilirubin \> 1\.5 × ULN.
•f. Serum creatinine \>1\.5 × ULN for age.
•g. International normalized ratio or prothrombin time (PT) \>ULN (\>1\.5 × ULN if on prophylactic reversible anticoagulants).
•2\. Patient has a QTcF \>470 msec. Patient has a familial or personal history of prolonged QT syndrome or Torsades de pointes.
•3\. Patient has clinically significant, uncontrolled cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association (NYHA) classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension (\>95th percentile for age), or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (eg, Type II second degree heart block or third\-degree heart block).