A Study of Avapritinib in Pediatric Patients With Solid Tumors Dependent on KIT or PDGFRA Signaling
- Conditions
- Solid Tumors Dependent on KIT or PDGFRA SignalingTherapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-508617-16-00
- Lead Sponsor
- Blueprint Medicines Corp.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 37
Patient must be 2 to < 18 years of age at the time of signing the informed consent., Confirmed diagnosis of R/R solid tumor, including CNS tumors, 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 Participant has confirmed diagnosis of DMG-H3K27a (confirmed by local testing of tumor sample) that has failed standard therapy or for which no standard therapy that may convey clinical benefit exists, as judged by the investigator., Participants with CNS disease should be on a stable (= 10% change) or decreasing dose of corticosteroids for at least 7 days prior to first dose of avapritinib, with no plans for dose escalation., Disease extent: a. 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. This is missing the criterion for Part 2 b. Part 2: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or RANO (for CNS tumors). For Participants 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 Participants 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 must have a Lansky (<16 years of age) or Karnofsky (=16 years of age) score of at least 50., Participant agrees to utilize contraception consistent with local regulations. - Male participants: Are vasectomized, or agree to use condoms, as defined in Section 5.4.2, from the start of Screening until 6 weeks after the last dose of study treatment, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant, see Section 5.4.2), or have a female partner who is NOT of childbearing potential. -Female participants: Agree to use effective contraception, as defined in Section 5.4.2, from the start of Screening until 6 weeks after the last dose of study treatment and have a male partner who uses a condom, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant), or have a male partner who is vasectomized with confirmed azoospermia., Participant can give written informed consent/assent before any study-specific Screening procedures (if feasible). Parental/legal guardian consent will be determined by local, regional, and/or national guidelines.
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)., Female subjects of childbearing potential who are unwilling, if not postmenopausal 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., Patient is pregnant, as documented by a serum ß-hCG pregnancy test consistent with pregnancy obtained at Screening and within 72 hours before the first dose of study treatment. Patients with ß-hCG values that are within the range for pregnancy but are notpregnant (false-positives) may be enrolled with written consent of the Sponsor after pregnancy has been ruled out. Female subjects of nonchildbearing potential (premenarchal, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) do not require a serum ß-hCG test., Patient is breastfeeding., Patient has prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator’s opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results., History of thrombosis requiring treatment within the past 6 months. This exclusion does not apply to catheter-related thrombosis if the catheter has been removed and did not require any other treatment in the previous 3 months., Patients who require anticoagulants, with the exception of stable doses of prophylactic reversible anticoagulants., Patients who are unable to swallow tablets (in Part 1) or minitablets (in Part 2) within the sprinkle capsules., Patients with a known risk of intracranial bleeding, such as a brain aneurysm that has not been removed or repaired, or a history of intracranial bleeding within the past year, or radiographic evidence of hemorrhage on Screening MRI. Exceptions are: patients with primary CNS tumors (provided they have not had CNS bleeding within 2 weeks of the first dose of avapritinib) or patients with punctate hemorrhages < 3 mm., History of a seizure disorder that is not well controlled on current antiepileptic medications., Patient is unwilling or unable to comply with scheduled visits, treatment administration plan, laboratory tests, or other study procedures and study restrictions., Patient has a QTcF >470 msec. Patient has a familial or personal history of prolonged QT
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method