A Study of Avapritinib in Pediatric Patients with Solid Tumors Dependent on KIT or PDGFRA Signaling

Phase 1

• Conditions: Solid Tumors Dependent on KIT or PDGFRA Signaling; MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-005234-15-IT
• Lead Sponsor: BLUEPRINT MEDICINES CORPORATIO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-01-26
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

- Patient is 2 to <18 years of age at the time the parent/guardian signs the Informed Consent Form.
- Confirmed diagnosis of a R/R solid tumor with a mutation (including non-synonymous point mutations, insertions, and deletions) in KIT or PDGFRA that has progressed despite standard therapy and no alternative treatment options are available OR Confirmed diagnosis of H3K27M mutant glioma 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.
-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 H3K27M mutant glioma or KIT/PDGFRA mutant 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. For patients with H3K27M mutant gliomas 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:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Pt has any of the following within 14 days before the first dose of study treatment: a. Platelet count <75 × 109/L (<100 × 109/L if a CNS tumor) with no platelet transfusion within 14 days prior to the measurement. b. Absolute neutrophil count <1.0 × 109/L. c. Hemoglobin <8.0 g/dL with no RBC transfusion minor/=7 days prior to the measurement. d. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × the upper limit of normal (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 >1.5 mg/dL 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 >ULN (>1.5 × ULN if on prophylactic reversible anticoagulants). 2. Pt has a QT interval corrected using Fridericia's formula (QTcF) >470 msec. Pt has a familial or personal history of prolonged QT syndrome or Torsades de pointes. 3. Pt has clinically significant, uncontrolled cardiovascular disease including congestive heart failure Grade III or IV according to the NYHA classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension, or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation. 4. Pt received the following systemic antineoplastic therapies: a. Systemic antineoplastic therapy. b. Focal external beam radiotherapy. Systemic radiopharmaceuticals, including nonstereotactic radiosurgery. Craniospinal irradiation. c. All AEs related to other antineoplastic therapies must have resolved to Grade 1 (Grade = 2 for peripheral neuropathy and/or ototoxicity) prior to the first dose of avapritinib. 5. Pt has previously received treatment with avapritinib. 6. Pt received autologous stem cell transplant (SCT) following myeloablative therapy or chimeric antigen receptor T cell (CAR-T) therapy within 3 months prior to the first dose of avapritinib or prior allogeneic SCT at any time. Patients who received stem cell reinfusion following non-myeloablative therapy are eligible once they meet the peripheral blood count criteria in Exclusion Criterion #1. 7. Pt requires ongoing treatment or has received treatment within 28 days before the start of avapritinib administration with drugs or foods that are strong CYP3A inhibitors or inducers. 8. Pt has had a major surgical procedure within 14 days of the first dose of study treatment. 9. Pt has a history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of avapritinib. 10. Female subjects of childbearing potential who are unwilling, if not post-menopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Male subjects who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Refer to Section 5.4.2 for acceptable methods of contraception. Please Refer to protocol for further information.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified