Olutasidenib + Temozolomide for Brain Tumors

Recruiting at 17 trial locations

Overseen By Vanessa Tan

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Rigel Pharmaceuticals

Must be taking: Temozolomide

Must not be taking: Investigational drugs, Anticonvulsants, Anticoagulants

Disqualifiers: Pregnancy, HIV, Metastatic HGG, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug combination Olutasidenib and Temozolomide for brain tumors?

Temozolomide has shown effectiveness in treating various brain tumors, including gliomas and oligodendroglial tumors, as it is a chemotherapy drug that can help shrink tumors. It has been used successfully in combination with other drugs, like olaparib, for certain types of gliomas, although side effects like fatigue and gastrointestinal issues are common. ^{1 2 3 4 5}

Is the combination of Olutasidenib and Temozolomide safe for treating brain tumors?

Temozolomide is generally well tolerated, but common side effects include fatigue, gastrointestinal issues, and blood-related problems. Some patients may experience skin reactions or need to reduce their dose due to these side effects. ^{1 2 3 6 7}

What makes the drug Olutasidenib + Temozolomide unique for treating brain tumors?

The combination of Olutasidenib and Temozolomide is unique because it targets brain tumors with a novel approach by combining Olutasidenib, which may have specific effects on tumor cells, with Temozolomide, a well-known chemotherapy drug that has shown effectiveness in treating various brain tumors. This combination could potentially offer a new treatment option for patients with certain types of brain tumors. ^{1 2 3 4 8}

Research Team

Santosh Valvi, FRACP, MSc

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

Nicholas G Gottardo, MB FRACP PhD

Principal Investigator

Perth Children's Hospital

Eligibility Criteria

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

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

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

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

Trial Timeline

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

Treatment Details

Interventions

• Olutasidenib (Anti-tumor agent)
• Temozolomide (Alkylating agent)

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.

Participant Groups

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.

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+

Findings from Research

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]

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]

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]

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, 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. [2019]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series. [2023]

4. England 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. [2020]

5. United States 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. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of temozolomide in patients with progressive low-grade glioma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Urticarial hypersensitivity reaction caused by temozolomide. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Activity of temozolomide in the treatment of central nervous system tumor xenografts. [2018]