A Phase 2, Multicenter, Clinical Study to Evaluate the Efficacy and Safety of Safusidenib Erbumine in Patients With Isocitrate Dehydrogenase 1 (IDH1) Mutant Glioma

Status: Recruiting
Location: See all (31) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

This is a 2-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 3 astrocytoma with high-risk features or Grade 4 IDH1-mutant astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Part 2 will be randomized, double blind, and placebo controlled.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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.

⁃ 4\. 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.

⁃ 5\. Patient has received no more than 2 prior therapies for disease recurrence/progression.

⁃ 6\. Patient has disease recurrence or progression or cannot tolerate the most recent therapy.

⁃ 7\. 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.

• Diagnosis of histologically confirmed IDH1-mutant Grade 3 with high risk features or Grade 4 astrocytoma, per WHO 2021 classification and Investigator Assessment.

• Have an IDH1 mutation (R132H/C/G/S/L) based on IHC (R132H only), polymerase chain reaction (PCR), or next-generation sequencing (NGS). CDKN2A/B status and at least 1 of the following must be confirmed: absence of 1p19q co-deletion by fluorescence in situ hybridization, array comparative genomic hybridization, or NGS; presence of an ATRX loss of function mutation by NGS; or loss of normal ATRX expression by IHC. A validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory must be used for all of the aforementioned results. Documentation of biomarker status, including redacted molecular pathology and NGS reports, must be provided during Screening.

• Must not have experienced disease recurrence or disease progression.

• Participants must have completed radiation therapy with a minimum of 90% of planned treatment completed (with or without concurrent temozolomide) and between 6 and 12 cycles of adjuvant temozolomide and have no evidence of disease progression. Randomization must occur at least 28 days and not more than 75 days after the final dose of temozolomide.

• 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.

• Has adequate hematologic and organ functions

Locations
United States
Alabama
University of Alabama
NOT_YET_RECRUITING
Birmingham
Arizona
Mayo Clinic - Arizona
NOT_YET_RECRUITING
Phoenix
St. Joseph's Hospital and Medical Center
RECRUITING
Phoenix
California
University of California, Los Angeles
NOT_YET_RECRUITING
Los Angeles
Hoag Memorial Hospital Presbyterian
NOT_YET_RECRUITING
Newport Beach
Stanford University
NOT_YET_RECRUITING
Palo Alto
University of California
NOT_YET_RECRUITING
San Francisco
Colorado
University of Colorado Health Cancer Care
NOT_YET_RECRUITING
Aurora
Connecticut
Yale University
RECRUITING
New Haven
Florida
University of Florida Health
NOT_YET_RECRUITING
Gainesville
Mayo Clinic - Florida
NOT_YET_RECRUITING
Jacksonville
University of Miami Health
NOT_YET_RECRUITING
Miami
Orlando Health Cancer Institute
NOT_YET_RECRUITING
Orlando
Kansas
University of Kansas Medical Center
NOT_YET_RECRUITING
Kansas City
Massachusetts
Dana-Farber Cancer Institute
RECRUITING
Boston
Massachusetts General Hospital
NOT_YET_RECRUITING
Boston
Michigan
Henry Ford Hospital
NOT_YET_RECRUITING
Detroit
Minnesota
Mayo Clinic - Rochester
RECRUITING
Rochester
Missouri
Washington University
NOT_YET_RECRUITING
St Louis
North Carolina
Duke Cancer Institute
RECRUITING
Durham
New Jersey
Rutgers Cancer Institute
RECRUITING
New Brunswick
New York
Columbia University Medical Center
RECRUITING
New York
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
New York University Langone Health
NOT_YET_RECRUITING
New York
Ohio
Cleveland Clinic
RECRUITING
Cleveland
Texas
University of Texas Southwestern Medical Center
NOT_YET_RECRUITING
Dallas
MD Anderson Cancer Center
NOT_YET_RECRUITING
Houston
Utah
Huntsman Cancer Insititute, University of Utah
RECRUITING
Salt Lake City
Virginia
UVA Health, Emily Couric Clinical Cancer Cente
RECRUITING
Charlottesville
Washington
Fred Hutch Cancer Center
NOT_YET_RECRUITING
Seattle
Wisconsin
University of Wisconsin Health
NOT_YET_RECRUITING
Madison
Contact Information
Primary
Clinical Trials at Nuvation Bio
ClinicalTrials@nuvationbio.com
332-208-6102
Time Frame
Start Date: 2023-06-05
Estimated Completion Date: 2028-03-01
Participants
Target number of participants: 125
Treatments
Experimental: safusidenib 125mg bid (part 1)
safusidenib 125mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.
Experimental: safusidenib 250mg bid (part 1)
safusidenib 250mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.
Experimental: safusidenib 500mg qd (part 1)
safusidenib 500mg qd administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.
Experimental: safusidenib 375mg bid (part 1)
safusidenib 375mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.
Experimental: safusidenib 500mg bid (part 1)
safusidenib 500mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.
Experimental: safusidenib 250mg bid (Part 2)
safusidenib administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment until disease progression or another reason for discontinuation occurs.
Placebo_comparator: placebo (Part 2)
Placebo administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with placebo until disease progression or another reason for discontinuation occurs.
Sponsors
Leads: Nuvation Bio Inc.
Collaborators: AnHeart Therapeutics Inc.

This content was sourced from clinicaltrials.gov

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