SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance)
United States365 participantsStarted 2023-06-05
Plain-language summary
This is a 3-part study. The purpose of Part 1 of the study is to evaluate the efficacy, safety, and pharmacokinetic (PK) characteristics of safusidenib in participants with recurrent/progressive IDH1-mutant World Health Organization (WHO) Grade 2 or Grade 3 glioma.
The purpose of Part 2 will be to evaluate the efficacy of maintenance safusidenib treatment versus placebo in IDH1-mutant Grade 2 or Grade 3 astrocytoma with high-risk features or IDH1-mutant Grade 4 astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Part 2 will be randomized, double-blind, and placebo-controlled.
The purpose of Part 3 will be to evaluate the efficacy of safusidenib in participants with residual or recurrent IDH1-mutant Grade 3 oligodendroglioma who have received surgery as their only treatment. Part 3 will be an open-label single-arm cohort and will enroll participants concurrently with Part 2.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
β. Patient must be β₯ 18 years of age at the time of signing the informed consent form (ICF).
β. Patient must have histologically confirmed recurrent or progressive WHO Grade 2 glioma or Grade 3 glioma with IDH1 R132H or R132C mutation confirmed by immunohistochemistry or molecular genetic testing.
β. The IDH mutation, and other applicable gene/molecular alterations (see Table 10-2) are determined by a validated assay as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified/College of American Pathologists (CAP)-accredited or locally equivalent clinical laboratories. Prior clinical pathology report fulfilling the diagnosis criteria prior to screening with tumor samples collected is acceptable for patient enrollment in both Part 1 and Part 2.
β. Patient has received no more than 2 prior therapies for disease recurrence/progression.
β. Patient has disease recurrence or progression or cannot tolerate the most recent therapy.
β. Patient must have a measurable lesion(s) as per the RANO-HGG criteria for primarily enhancing lesions or RANO-LGG criteria for primarily non-enhancing lesions. The lesion (s) must be visible on 2 or more axial slices and have perpendicular diameters of at least 10 Γ 10 mm. The definition of primarily enhancing lesions or primarily non-enhancing lesions is referred to Section 8.3.1.
β. Must be β₯18 years old at the time of signing the ICF.
What they're measuring
1
Part 1: Incidence of adverse events (AEs) and serious adverse events (SAEs)
Timeframe: From participants sign ICF to 30 days after last doseοΌaverage 2 years
2
Part 2: Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) per Response Assessment in Neuro-Oncology (RANO) 2.0
Timeframe: From randomization until the date of first documented disease progression, average 2 years
3
Part 3 Objective Response Rate (ORR) (Complete Response (CR), Partial Response (PR) and Minor Response (MR)) assessed by Blinded Independent Central Review (BICR) per Response Assessment in Neuro-Oncology (RANO) 2.0
Timeframe: From the first dose of study drug until the date of first documented disease progression, average 18 months
β. Must agree to submit sufficient tumor tissue for retrospective biomarker and histological analyses. This requirement may be waived in rare circumstances with approval by the Sponsor.
Exclusion criteria
β. Prior anti-cancer therapy, within the applicable periods shown below, before the start of the protocol treatment:
β. Systemic drug therapies: within 3 weeks (lomustine within 6 weeks)
β. Surgery: within 3 weeks
β. Radiation therapy: within 12 weeks
β. Investigational agents: within 5 half-lives for other investigational agents
β. Patient did receive the prior therapy targeted to IDH1 mutation..
β. Known hypersensitivity to safusidenib or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of safusidenib.
β. Participants with prior or anticipated treatment with anti-angiogenic agents such as Avastin (bevacizumab), agents known to target IDH1 or IDH2, or investigational agents for glioma are excluded.