Olutasidenib + Temozolomide for Brain Tumors

Recruiting at 19 trial locations

Overseen By Vanessa Tan

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Rigel Pharmaceuticals

Must be taking: Temozolomide

Must not be taking: Investigational drugs, Anticonvulsants, Anticoagulants

Disqualifiers: Pregnancy, HIV, Metastatic HGG, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining olutasidenib (a potential new drug) and temozolomide (a chemotherapy drug) can extend survival for individuals diagnosed with high-grade glioma (HGG) featuring a specific genetic change known as an IDH1 mutation. It targets various types of these brain tumors, including aggressive forms originating in the brain or spinal cord. Participants must be newly diagnosed with an IDH1-mutant brain tumor and meet specific criteria, such as having a tumor in certain brain or spine areas. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but certain medications are not allowed. You cannot take other investigational drugs, certain anti-cancer agents, strong enzyme-inducing anticonvulsants, strong CYP3A4/5 inducers, medications that prolong the QTc interval, or therapeutic anticoagulation with warfarin. Corticosteroids are allowed, and SSRIs should be used with caution.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that olutasidenib is generally well-tolerated by patients with certain brain tumors. In studies involving patients whose gliomas (a type of brain tumor) returned or did not respond to treatment, taking 150 mg of olutasidenib twice daily was safe and showed early signs of effectiveness. These patients had tumors with a specific change in the IDH1 gene, similar to the change targeted in the current trial.

Temozolomide, often called TMZ, is a chemotherapy drug already approved and commonly used for brain tumors. Its safety profile is well-known, and it is usually well-tolerated, though it can cause side effects like nausea and tiredness, common with many chemotherapy drugs.

The current trial tests a combination of olutasidenib and temozolomide to determine their effectiveness in treating high-grade gliomas with an IDH1 mutation. The goal is to leverage the strengths of both drugs while carefully monitoring safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for brain tumors, which often includes surgery, radiation, and chemotherapy, olutasidenib combined with temozolomide specifically targets IDH-1 mutations found in certain types of brain tumors. This combination is promising because olutasidenib inhibits the mutated IDH-1 enzyme, potentially slowing or stopping tumor growth at the molecular level. Researchers are excited about these treatments because they offer a more targeted approach, which could lead to better outcomes and fewer side effects compared to traditional, broad-spectrum therapies.

What evidence suggests that this trial's treatments could be effective for high-grade glioma?

This trial will evaluate the combination of olutasidenib with temozolomide (TMZ) for treating aggressive brain tumors called high-grade gliomas (HGG) in children and young adults with a specific genetic change known as an IDH1 mutation. Research has shown that olutasidenib is generally safe and has demonstrated early signs of effectiveness in patients whose tumors have returned or not responded to treatment. Temozolomide is a well-known chemotherapy drug used for brain tumors. This combination targets the IDH1 mutation, which is believed to promote tumor growth. Early results suggest that this treatment could potentially extend the lives of patients with these specific brain tumors. Participants in this trial will be assigned to different strata based on their specific type of IDH1 mutant brain tumor. ^{1 2 3 4 6}

Who Is on the Research Team?

Santosh Valvi, FRACP, MSc

Principal Investigator

Perth Children's Hospital

Nicholas G Gottardo, MB FRACP PhD

Principal Investigator

Perth Children's Hospital

Michael J Fisher, MD

Principal Investigator

Children's Hospital of Philadelphia

Maryam Fouladi, MD

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for young patients aged between 1 and 39 with a high-grade glioma brain tumor that has an IDH1 mutation. They must have good liver, bone marrow, and kidney function, be able to give informed consent, and not be pregnant or breastfeeding. Patients must agree to use effective contraception if applicable.

Inclusion Criteria

My bone marrow is working well.

My brain tumor is newly diagnosed and has an IDH1 mutation.

My cancer has a specific change in the IDH1 gene.

Exclusion Criteria

Patients with malignancy related to HIV or solid organ transplant are not eligible

I do not have a condition that affects how my body absorbs medication.

I am not on any cancer treatments except possibly temozolomide with radiation therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy

Participants receive focal radiotherapy as part of the initial treatment

Varies

Treatment

Participants receive maintenance therapy with olutasidenib and temozolomide for 13 cycles followed by 13 cycles of single agent olutasidenib

24 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Olutasidenib
• Temozolomide

Trial Overview The study tests the effectiveness of olutasidenib combined with temozolomide (TMZ) in extending the lives of patients with IDH-mutant high-grade gliomas. It aims to see if this drug combination can improve survival rates in these young patients.

How Is the Trial Designed?

Group I: Stratum C Experimental Treatment 1 Intervention

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

Group II: Stratum B Experimental Treatment 1 Intervention

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

Group III: Stratum A Experimental Treatment 1 Intervention

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

Olutasidenib is already approved in United States for the following indications:

Approved in United States as Rezlidhia for:

• Acute Myeloid Leukemia (AML) with a susceptible IDH1 mutation

Who Is Running the Clinical Trial?

Rigel Pharmaceuticals

Lead Sponsor

Trials

37

Recruited

4,000+

Nationwide Children's Hospital

Collaborator

Trials

354

Recruited

5,228,000+

Published Research Related to This Trial

In a phase II trial involving 46 patients with progressive low-grade glioma, Temozolomide (Temodar) demonstrated a 61% objective response rate, with 24% achieving complete response and 37% achieving partial response.

The treatment showed promising safety, with limited toxicity observed; however, one patient experienced severe complications, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of temozolomide in patients with progressive low-grade glioma. Quinn, JA., Reardon, DA., Friedman, AH., et al.[2022]

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

Temozolomide, an oral medication used for treating glioblastoma and anaplastic astrocytoma, is generally well tolerated with limited dermatologic side effects.

However, this report highlights the first case of urticarial hypersensitivity reaction caused by temozolomide, emphasizing the need for awareness of potential skin reactions as its use increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urticarial hypersensitivity reaction caused by temozolomide. Pothiawala, S., Hsu, MY., Yang, C., et al.[2018]

In a study of 20 patients with various types of glioma, the combination of olaparib and temozolomide (TMZ) showed a 50% objective radiographic response rate in patients with recurrent IDH-mutant grade 2-3 gliomas, indicating potential efficacy for this specific group.

While the treatment was generally manageable, common side effects included fatigue and gastrointestinal issues, with 30% of patients requiring dose adjustments due to toxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series. Schaff, LR., Kushnirsky, M., Lin, AL., et al.[2023]

In a phase II trial involving 38 patients with recurrent oligodendroglial tumors, temozolomide (TMZ) demonstrated a high response rate, with 52.6% of patients showing a complete or partial response, indicating its efficacy as a first-line chemotherapy.

TMZ was generally well tolerated, with hematologic side effects being the most common, and only one patient discontinuing treatment due to toxicity, suggesting a favorable safety profile for chemotherapy-naive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971. van den Bent, MJ., Taphoorn, MJ., Brandes, AA., et al.[2022]

In a phase II trial involving 32 patients with recurrent oligodendroglial tumors, temozolomide (TMZ) demonstrated a 25% objective response rate, indicating its potential as an effective second-line treatment after PCV chemotherapy.

TMZ was generally well tolerated, with hematological side effects being the most common, and a median time to progression of 8 months for those who responded, suggesting it could be a viable option for patients who do not respond to initial treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972. van den Bent, MJ., Chinot, O., Boogerd, W., et al.[2020]

Temozolomide showed significant effectiveness in treating various central nervous system cancers, including ependymoma and high-grade gliomas, with growth delays in tumors being 1.8-7.5 times greater than those produced by procarbazine.

The treatment resulted in impressive increases in median survival rates, such as 1285% for adult glioma and 323% for childhood glioma, indicating its potential as a powerful therapeutic option for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of temozolomide in the treatment of central nervous system tumor xenografts. Friedman, HS., Dolan, ME., Pegg, AE., et al.[2018]

In a study of 32 patients with brain metastases from solid tumors, the combination of temozolomide (TMZ) and cisplatin (CDDP) showed promising efficacy, with a 28.1% partial response rate and a median overall survival of 5.5 months.

The treatment was generally well-tolerated, although some patients experienced grade III-IV toxicities, including anemia and leukopenia, indicating that while the regimen is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study. Christodoulou, C., Bafaloukos, D., Linardou, H., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06161974

Study of Olutasidenib and Temozolomide in HGG 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9825299/

Olutasidenib (FT-2102) in patients with relapsed or refractory ... Olutasidenib 150 mg BID was well tolerated in patients with relapsed/refractory gliomas harboring an IDH1 R132X mutation and demonstrated preliminary evidence ...

3. trials.braintumor.org trials.braintumor.org/trials/NCT06161974

Study of Olutasidenib and Temozolomide in HGG 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 ...

4. cincinnatichildrens.org cincinnatichildrens.org/service/c/clinical-trials/studies/TarGeT-D-060325

Study of Olutasidenib and Temozolomide in HGG 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 ...

5. researchgate.net researchgate.net/publication/361007632_Olutasidenib_FT-2102_in_patients_with_relapsed_or_refractory_IDH1-mutant_glioma_a_multicenter_open-label_phase_1b2_trial

(PDF) Olutasidenib (FT-2102) in patients with relapsed or ... Grade 3‒4 adverse events (≥10%) included alanine aminotransferase increased and aspartate aminotransferase increased (three [12%], each). Conclusions: ...

6. nationwidechildrens.org nationwidechildrens.org/research/clinical-research/cancer-clinical-research/neurooncology-studies/target-d

Patients With IDH-mutant HGG Study Olutasidenib is a medicine taken by mouth that targets the mutated IDH1 protein in the brain. It has shown to be safe and somewhat effective in adults with ...