A Drug-drug Interaction Study to Investigate the Effect of Avapritinib on the Pharmacokinetics of Midazolam in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors (GIST) and Other Advanced Solid Tumors

  • STATUS
    Recruiting
  • End date
    Dec 31, 2023
  • participants needed
    20
  • sponsor
    Blueprint Medicines Corporation
Updated on 12 October 2022

Summary

The purpose of this study is to investigate the effect of multiple dosing of avapritinib on the pharmacokinetics (PK) of midazolam in adult patients with metastatic or unresectable gastrointestinal stromal tumors (GIST), recurrent gliomas, or other KIT mutant tumors.

Details
Condition Gastrointestinal Stromal Tumors, GIST, Non-resectable Advanced Solid Tumors, Recurrent or Unresectable Central Nervous System (CNS) Tumors
Treatment Midazolam, Avapritinib
Clinical Study IdentifierNCT04908176
SponsorBlueprint Medicines Corporation
Last Modified on12 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Must be ≥18 years of age at the time of signing the informed consent
Confirmed diagnosis of
metastatic or unresectable KIT mutant GIST that has recurred or progressed after at least 4 lines of prior systemic SOC therapy or the Investigator has determined that treatment with SOC therapy is not appropriate for patients who failed at least 2 lines of prior SOC
OR
--Non-resectable advance solid tumor with KIT mutation with progression following
standard of care treatment
OR
--Confirmed diagnosis of recurrent or unresectable CNS tumors including :IDH-mutant
astrocytoma, IDH-mutant oligodendroglioma, glioblastoma, H3K27-altered diffuse midline
glioma, H3G34-mutant diffuse hemispheric glioma, midline glioma (with unknown H3K27
mutation status) that has failed prior radiation or systemic SOC therapy
Must be able to swallow an oral medication
Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Patient agrees to use contraception consistent with local regulations
Must provide signed informed consent to participate in the study

Exclusion Criteria

Patients with GIST that harbors a known PDGFRA mutation
Known hypersensitivity to avapritinib, midazolam, or any of their excipients
Have received previous therapy with avapritinib
Have any of the following laboratory abnormalities before the first dose of study
drug
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >3 × upper
limit of normal (ULN) if no hepatic metastases are present; >5 × ULN if hepatic
metastases are present
Total bilirubin >1.5 × ULN; >3 × ULN in the presence of Gilbert's Disease
Estimated (Cockcroft-Gault formula) or measured creatinine clearance <60 mL/min
Platelet count <100 × 10^9/liter (L)
Absolute neutrophil count (ANC) <1.0 × 10^9/L
Hemoglobin <9 grams per deciliter (g/dL). Transfusion and erythropoietin may be
used to reach at least 9 g/dL but must have been administered at least 2 weeks
before the first dose of the study drug
Require therapy with a concomitant medication that is a strong and moderate CYP3A4
inhibitors or inducers
Consumption of any nutrients known to modulate CYP3A4 enzymes activity (eg, grapefruit
or grapefruit juice, pomelo juice, star fruit, or Seville [blood] orange and
derivative products, cruciferous vegetables [eg, broccoli, cauliflower, cabbage
brussel sprouts]) within 14 days before screening and during the study until the end
of the Main Treatment Period
Have received a prior anticancer drug less than 5 half-lives or 14 days (whichever is
shorter) before screening
Have had a major surgical procedure within 14 days of the first dose of study drug or
have significant traumatic injury within 28 days before screening
Have history of a cerebrovascular accident or transient ischemic attacks within 1 year
before screening
Have known risk of intracranial bleeding, such as a brain aneurysm or history of
subdural or subarachnoid bleeding
Have corrected QT interval using Fridericia's formula (QTcF) >450 msec
Have clinically significant, uncontrolled, cardiovascular disease, including
congestive heart failure Grades 2, 3, or 4 according to the New York Heart Association
classification, myocardial infarction, or unstable angina within the previous 6
months, or uncontrolled hypertension
Have experienced any hemorrhage or bleeding event National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade ≥3 within 4
weeks before screening. Exceptions are patients with primary CNS tumors who are
eligible if the Grade ≥3 bleeding event was in the CNS and it occurred 2 weeks or more
prior to the first dose of avapritinib
Patients who have a symptomatic nonhealing wound, ulcer, GI perforation, or bone
fracture
Have received organ or allogenic bone marrow or peripheral blood stem cell transplant
Have known diagnosis of human immunodeficiency virus infection or active viral
hepatitis; viral testing is not required
History of alcohol consumption exceeding 2 standard drinks per day on average (1
standard drink = 14 grams of alcohol). Alcohol consumption will be prohibited 48 hours
before screening and throughout the entire the Main Treatment Period
Use of tobacco- or nicotine-containing products within 3 months of enrollment
Is a female patient who is 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 until at least 6 weeks after the last dose of study drug
Males 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 drug
Is a female patient who is pregnant, as documented by a serum beta human chorionic
gonadotropin (β-hCG) pregnancy test consistent with pregnancy obtained within 7 days
before the first dose of study drug. Patients with β-hCG values that are within the
range for pregnancy but are not pregnant (false positives) may be enrolled with
written consent of the Sponsor after pregnancy has been ruled out. Females of
nonchildbearing potential (postmenopausal for more than 12 months, bilateral tubal
ligation, bilateral oophorectomy, or hysterectomy) do not require a serum β-hCG test
Female who is breastfeeding
Have a 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 drugs, or impair the assessment of study results
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