SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance)
United States, Australia, China365 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 range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Patient must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
. 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.
. 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.
. Patient has received no more than 2 prior therapies for disease recurrence/progression.
. Patient has disease recurrence or progression or cannot tolerate the most recent therapy.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Since this is a Phase 3 trial testing safusidenib specifically for IDH1-mutant gliomas, and my tumor has an IDH1 mutation, is the maintenance therapy approach being studied here something that would fit where I am in my treatment right now — and how does it compare to what standard care would look like for me?
2The trial has three parts measuring different things — safety first, then progression-free survival, then response rates — so which part would I likely be entering, and what does that mean for how much is already known about the drug's safety and effectiveness at this stage?
3Progression-free survival is being measured using RANO 2.0 criteria with independent reviewers, which means regular brain imaging will be involved — how often would I need scans and clinic visits, and is that level of commitment realistic given my current health and daily life?
4Since this trial is specifically for IDH1-mutant glioma and my pathology report shows an IDH1 mutation, are there other subtypes of my diagnosis — like whether I have a grade 2, 3, or 4 astrocytoma, or an oligodendroglioma — that might affect whether this trial would or wouldn't be a good fit for me?
5Are there any signals from earlier-phase IDH1 inhibitor research that you think are worth discussing before I consider this trial, particularly around side effects, and how would joining this study affect my access to other treatments if my disease progresses while I'm on it?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
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 dose，average 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
. 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 × 10 mm. The definition of primarily enhancing lesions or primarily non-enhancing lesions is referred to Section 8.3.1.
. Must be ≥18 years old at the time of signing the ICF.
. 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
. Prior anti-cancer therapy, within the applicable periods shown below, before the start of the protocol treatment:
. Systemic drug therapies: within 3 weeks (lomustine within 6 weeks)
. Surgery: within 3 weeks
. Radiation therapy: within 12 weeks
. Investigational agents: within 5 half-lives for other investigational agents
. Patient did receive the prior therapy targeted to IDH1 mutation..
. Known hypersensitivity to safusidenib or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of safusidenib.
. 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.