Study on the Safety and Effectiveness of Vorasidenib and Temozolomide for Patients with IDH1 or IDH2 Mutant Glioma

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What is this study about?

This clinical trial is focused on studying a type of brain tumor called glioma, which has specific genetic changes known as IDH1 or IDH2 mutations. The study will test a combination of two treatments: vorasidenib and temozolomide. Vorasidenib is a new medication being tested, while temozolomide is a chemotherapy drug already used to treat brain tumors. The purpose of the study is to evaluate how safe and tolerable vorasidenib is when used with temozolomide and to see how effective this combination is in treating gliomas with these mutations.

Participants in the study will receive the medications in the form of capsules or tablets taken by mouth. The study will be conducted in two phases. In the first phase, the focus will be on determining the best dose of vorasidenib to use with temozolomide. In the second phase, the study will look at how well the combination works in controlling the tumor over a period of time. The study will also monitor the participants for any side effects or adverse reactions to the treatment.

The study aims to gather information on the progression of the disease and the overall survival of participants. It will also measure the levels of vorasidenib and its breakdown products in the blood, as well as the levels of temozolomide. The study is expected to continue until early 2028, with recruitment of participants starting in 2025. This research is important for understanding how these treatments can be used together to potentially improve outcomes for patients with IDH1 or IDH2 mutant gliomas.

1 initial assessment

Upon joining the study, an initial assessment will be conducted to confirm eligibility. This includes verifying age, weight, and medical history related to IDH1 or IDH2-mutant glioma.

Blood tests will be performed to check liver, kidney, and bone marrow function. A pregnancy test is required for female participants of reproductive potential.

2 treatment initiation

The treatment phase begins with the administration of two medications: vorasidenib and temozolomide.

Vorasidenib is taken orally in the form of film-coated tablets. The dosage and frequency will be determined by the study team.

Temozolomide is taken orally as hard capsules. The dosage and frequency will be specified by the study team.

3 treatment monitoring

Regular monitoring will occur throughout the treatment period to assess safety and tolerability. This includes checking for any side effects or adverse reactions.

Blood tests and other assessments will be conducted periodically to monitor the body’s response to the treatment.

4 follow-up assessments

Follow-up assessments will be conducted to evaluate the effectiveness of the treatment. This includes measuring progression-free survival, which is the length of time during and after treatment that the disease does not worsen.

Additional tests may be performed to gather information on the concentration of the medications in the blood and their effects.

5 completion of study

Upon completion of the study, a final assessment will be conducted to gather data on the overall outcomes and any long-term effects of the treatment.

Participants will be informed of the study results and any further steps, if necessary.

Who Can Join the Study?

Be at least 18 years old and weigh at least 40 kg.
Phase 1b ONLY: Have a confirmed diagnosis of Grade 2, 3, or 4 IDHm glioma, which is a type of brain tumor. For oligodendroglioma, there must be a specific genetic change called 1p19q co-deletion. For astrocytoma, there should be no 1p19q co-deletion and/or a change in the ATRX gene.
Phase 1b ONLY: Be suitable to receive TMZ (a type of chemotherapy) after radiotherapy or for the first recurrence of the disease, as judged by the doctor. If receiving TMZ after radiotherapy, treatment must start within 6 weeks after finishing radiotherapy.
Have good liver function, shown by specific blood test results: total bilirubin ≤1.5 times the normal limit, AST and ALT (liver enzymes) within normal limits, and alkaline phosphatase ≤2.5 times the normal limit.
Phase 2 ONLY: Have a confirmed diagnosis of Grade 4 astrocytoma, IDHm. Those with a specific genetic deletion called CDKN2A/B are eligible.
Phase 2 ONLY: Have no 1p19q co-deletion and/or a change in the ATRX gene, confirmed by local testing.
Phase 2 ONLY: Have received standard radiotherapy with concurrent TMZ before joining the study. Treatment must start within 6 weeks after completing this therapy.
Have a documented IDH1 or IDH2 mutation, confirmed by testing of tumor tissue.
Have good kidney function, defined as a creatinine clearance of at least 40 mL/min, which is a measure of how well the kidneys are working.
Have good bone marrow function, shown by specific blood test results: absolute neutrophil count ≥1,500/mm³, hemoglobin ≥9 g/dL, and platelets ≥100,000/mm³.
Have recovered from any significant side effects of previous cancer treatments, unless they are stable and manageable according to the doctor.
Have an expected survival of at least 3 months.
Have a Karnofsky Performance Status (KPS) of at least 70, which is a measure of the ability to carry out daily activities.
If taking corticosteroids (a type of medication) for glioma-related reasons, the dose must be stable or decreasing (no more than 4 mg/day of dexamethasone or equivalent) for at least 5 days before starting the study treatment.
Female participants who can have children must have a negative pregnancy test before starting the study treatment. This includes women who have started menstruating and have not had surgery to remove the uterus or ovaries, and are not naturally postmenopausal (have not had a period for 24 consecutive months).

Who Cannot Join the Study?

Patients with any other type of cancer besides IDH1-mutant Glioma or IDH2-mutant Glioma cannot participate.
Patients who have had a recent heart attack or have severe heart problems are not eligible.
Patients with uncontrolled high blood pressure cannot join the study.
Patients who are pregnant or breastfeeding are not allowed to participate.
Patients who have an active infection that requires treatment with antibiotics are excluded.
Patients who have had another investigational drug within the last 4 weeks cannot participate.
Patients with a history of allergic reactions to similar drugs are not eligible.
Patients who have a condition that affects their ability to absorb medications in the stomach or intestines cannot join the study.
Patients with severe liver or kidney disease are excluded from the trial.
Patients who have a history of drug or alcohol abuse within the past year are not eligible.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Oncopole Claudius Regaud	Toulouse	France
IRCCS Humanitas Research Hospital	Rozzano	Italy
Medical University Of Vienna	Vienna	Austria
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany

Other Sites

Site Name	City	Country
Istituto Oncologico Veneto	Padua	Italy
Hospital Universitario 12 De Octubre	Madrid	Spain
Universitaetsklinikum Regensburg AöR	Regensburg	Germany
Centre Hospitalier Lyon Sud	Pierre Benite	France
Hopital Beaujon	Clichy	France
Evdkkwt Ujeduvykkpwh Mbnapia Cyckzhv Ryzyxkzhl (hfisotb Mah	Rotterdam	The Netherlands
Atmvczd Ouulyygmuhz Uaeoqczgdhtgd Cnwjvtrnlqls Dhlep Sdxewa E Duzmw Setorpa Ds Tjqook	Turin	Italy
Htjyaook Vtoz didbbyoy	Barcelona	Spain

Trial status

Country	Status	Recruitment Start
Austria	Not recruiting	31.03.2025
France	Not recruiting	31.03.2025
Germany	Not recruiting	31.03.2025
Italy	Not recruiting	31.03.2025
Spain	Not recruiting	31.03.2025
The Netherlands	Not recruiting	31.03.2025

Trial locations

Investigated drugs:

Vorasidenib is a medication being studied for its potential to help treat a type of brain tumor called glioma, which has specific genetic changes known as IDH1 or IDH2 mutations. In this clinical trial, vorasidenib is being tested to see if it can be safely used together with another medication to improve treatment outcomes. The goal is to find out if this combination can help control the growth of the tumor and improve the patient’s condition.

Temozolomide (TMZ) is a well-known chemotherapy drug used to treat certain types of brain tumors. It works by damaging the DNA of cancer cells, which can stop them from growing and dividing. In this study, temozolomide is being used in combination with vorasidenib to see if the two medications together can be more effective in treating glioma with IDH1 or IDH2 mutations than temozolomide alone. The researchers are looking to see if this combination can help slow down the progression of the disease and improve survival rates for patients.

Investigated diseases:

Glioma

IDH1-mutant Glioma – IDH1-mutant glioma is a type of brain tumor characterized by a mutation in the isocitrate dehydrogenase 1 (IDH1) gene. This mutation leads to abnormal cell growth in the brain, forming a mass that can disrupt normal brain function. The disease typically progresses slowly, with tumor cells infiltrating surrounding brain tissue. Over time, the tumor may increase in size, causing symptoms such as headaches, seizures, and cognitive changes. The progression can vary, with some tumors remaining stable for extended periods. As the tumor grows, it can exert pressure on the brain, leading to more pronounced neurological symptoms.

IDH2-mutant Glioma – IDH2-mutant glioma is a brain tumor associated with a mutation in the isocitrate dehydrogenase 2 (IDH2) gene. This genetic alteration results in the uncontrolled proliferation of glial cells in the brain. The tumor typically grows slowly, infiltrating nearby brain tissue and potentially causing neurological symptoms. As the disease progresses, the tumor may enlarge, leading to increased intracranial pressure and associated symptoms such as headaches and seizures. The rate of progression can vary, with some tumors remaining indolent for years. Over time, the tumor’s growth can lead to significant disruption of normal brain function.

Trial ID:

2024-513738-39-00

Protocol code:

S095032-211

NCT ID:

NCT06478212

Trial Phase:

Human Pharmacology (Phase I) – Other

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Study on the Safety and Effectiveness of Vorasidenib and Temozolomide for Patients with IDH1 or IDH2 Mutant Glioma

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?