Study of Olutasidenib and Temozolomide in HGG

NCT06161974 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: TarGeT-D
• Study Type: interventional
• Target: 60
• Locations: 6 countries
• Sites: 18

Brief Summary

The goal of this study is to determine the efficacy of the study drug olutasidenib to treat newly diagnosed pediatric and young adult patients with a high-grade glioma (HGG) harboring an IDH1 mutation. The main question the study aims to answer is whether the combination of olutasidenib and temozolomide (TMZ) can prolong the life of patients diagnosed with an IDH-mutant HGG.

Conditions

High Grade Glioma; Astrocytoma; Astrocytoma, Grade III; Astrocytoma, Grade IV; Diffuse Intrinsic Pontine Glioma; WHO Grade III Glioma; WHO Grade IV Glioma; Metastatic Brain Tumor; Diffuse Midline Glioma, H3 K27M-Mutant; Thalamus Tumor; Spinal Tumor; IDH1 Mutation; IDH1 R132; IDH1 R132C; IDH1 R132H; IDH1 R132S; IDH1 R132G; IDH1 R132L; Oligodendroglioma

Outcome Measures

Primary Outcomes (3)

• Establish the RP2D of Olutasidenib and Temozolomide (Feasibility cohort)

  To identify the dose of olutasidenib that is feasible when given post-RT in combination with temozolomide as maintenance therapy in pediatric and young adult patients newly diagnosed with IDH1-mutant high-grade glioma

  Completion of cycle 1 (28 days) for 6-24 patients

• Assess Progression-Free Survival (PFS) in Grade 3 IDH1-mutant Astrocytoma (Stratum A)

  To assess the post-RT efficacy of olutasidenib in newly diagnosed patients with WHO Grade 3 IDH1-mutant Astrocytoma treated with maintenance olutasidenib and temozolomide for 13 cycles followed by 13 cycles of single agent olutasidenib compared to molecularly-stratified and matched historical controls

  From date of diagnosis until date of Progressive Disease or death due to any cause or date of last follow-up, assessed up 24 months

• Maximum plasma concentration [Cmax] of Olutasidenib

  To characterize the plasma pharmacokinetic (PK) properties of olutasidenib in pediatric patients (e.g., 12 to \< 18 years of age), administered in combination with temozolomide (first year) and as single agent (second year) as maintenance chemotherapy by measuring the Maximum Concentration \[Cmax\] and Area Under the Curve (AUC) of olutasidenib in plasma (All strata).

  From Day 1 of treatment until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 24 months

Secondary Outcomes (4)

• Evaluate objective response rate (ORR) in HGG (All Strata)

  From day 1 of protocol treatment through 30 days following end of protocol treatment

• Evaluate Health-Related Quality of Life Outcomes (All Strata)

  From pre-maintenance (2 weeks before the first cycle), and at the start of even numbered cycles (each cycle is 28 days) and at the End of Treatment visit (can have up to 26 cycles)

• Evaluate Overall Survival in IDH1-mutant Grade 3 Astrocytoma (Stratum A)

  From date of diagnosis until date of death due to any cause or date of last follow-up, assessed up to 60 months

• Assess Progression-Free Survival in IDH1-mutant Grade 4 Astrocytoma (Stratum B)

  From date of diagnosis until date of Progressive Disease or death due to any cause or date of last follow-up, assessed up 24 months

Study Arms (3)

Stratum A

EXPERIMENTAL

Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 3.

Drug: Olutasidenib + TMZ

Stratum B

EXPERIMENTAL

Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 4.

Drug: Olutasidenib + TMZ

Stratum C

EXPERIMENTAL

Patients with IDH-1 mutant DIPG, primary thalamic and spinal cord IDH-1 mutant HGG.

Drug: Olutasidenib + TMZ

Interventions

Olutasidenib + TMZ DRUG

Olutasidenib 150 mg PO BID + Temozolomide 200 mg/m2 PO QD

Stratum A; Stratum B; Stratum C

Eligibility Criteria

• Age: 12 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ) Age: patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR
• ) Diagnosis:
• Patients with a newly-diagnosed IDH1-mutant HGG including DIPG are eligible. All patients must have tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR.
• For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, and histopathology consistent with diffuse WHO Grade 2-4 glioma.
• All other HGG must be WHO Grade 3 or 4.
• ) Disease status: There are no disease status requirements for enrollment
• Measurable disease is not required. Patients without measurable disease are eligible.
• Primary spinal tumor: Patients with a primary spinal HGG are eligible.
• Patient must not have metastatic disease.
• Presence of at Least One Relevant Actionable Somatic Mutation in IDH1 Gene, Detailed Here:
• R132H, R132C, R132S, R132G or R132L.
• Patients whose tumors harbor other alterations in addition to IDH1 mutation will potentially be eligible following consensus recommendation by the international multidisciplinary molecular screening committee.
• Patients with IDH2 mutations are not eligible.
• Patients with oligodendroglioma, IDH-mutant and 1p/19q-codeleted are not eligible.
• Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

You may not qualify if:

• Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown potential risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy.
• A highly effective contraception method is defined as one that results in a low failure rate (\<1% per year) when used consistently and correctly. The following are considered highly effective contraception methods:
• Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation.
• Progesterone-only hormonal contraception associated with inhibition of ovulation.
• Intra Uterine Device (IUD).
• Intra uterine hormone releasing system.
• Bilateral tubal occlusion.
• Vasectomized partner.
• Sexual abstinence (avoiding heterosexual intercourse).
• The following contraceptive measures are NOT considered effective:
• Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation.
• Male or female condom with or without spermicide.
• Cap, diaphragm, or sponge with spermicide.
• Using the following types of concomitant medications:
• Corticosteroids: Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported.

Sponsors & Collaborators

• Rigel Pharmaceuticals: lead
• Nationwide Children's Hospital: collaborator

Study Sites (18)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

NOT YET RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

NOT YET RECRUITING

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

Susan Chi

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Duke University Health System

Durham, North Carolina, 27708, United States

NOT YET RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43235, United States

NOT YET RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

NOT YET RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

NOT YET RECRUITING

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

NOT YET RECRUITING

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

NOT YET RECRUITING

Perth Children's Hospital

Perth, Western Australia, 6000, Australia

NOT YET RECRUITING

The Hospital for Sick Children (SickKids)

Toronto, Ontario, M5G1X8, Canada

NOT YET RECRUITING

Montreal Children's Hospital

Montreal, Quebec, H4A3J1, Canada

NOT YET RECRUITING

Hopp Children's Cancer Center at NCT Heidelberg (KiTZ)

Heidelberg, Baden-Wurttemberg, 69120, Germany

NOT YET RECRUITING

Princess Máxima Center

Utrecht, 3720, Netherlands

NOT YET RECRUITING

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Glioma; Astrocytoma; Glioblastoma; Diffuse Intrinsic Pontine Glioma; Brain Neoplasms; Spinal Cord Neoplasms; Oligodendroglioma

Interventions

olutasidenib; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Santosh Valvi, FRACP, MSc

  Perth Children's Hospital

  STUDY CHAIR

• Nicholas G Gottardo, MB FRACP PhD

  Perth Children's Hospital

  STUDY CHAIR

• Michael J Fisher, MD

  Children's Hospital of Philadelphia

  STUDY CHAIR

• Maryam Fouladi, MD

  Nationwide Children's Hospital

  STUDY CHAIR

Central Study Contacts

Jill DeFratis Robinson

CONTACT

650-624-1100; jrobinson@rigel.com

Vanessa Tan

CONTACT

650-624-1100; clinicaltrials@rigel.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Olutasidenib +TMZ

Study Record Dates

• First Submitted: November 22, 2023
• First Posted: December 8, 2023
• Study Start: March 1, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2035
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); CA (2); US (10); AU (3); DE (1); GB (1)