Tirabrutinib vs Rituximab/Temozolomide for Brain Cancer

Overseen By Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ono Pharmaceutical Co. Ltd

Must not be taking: Corticosteroids, Bruton's inhibitors

Disqualifiers: Non-B-cell PCNSL, Systemic lymphoma, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

132 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new drug, tirabrutinib, compared to a combination of rituximab (an immunotherapy) and temozolomide (a chemotherapy drug) for treating relapsed or refractory primary central nervous system lymphoma (PCNSL). The study aims to determine which treatment better controls the cancer and assesses their safety for patients. Individuals with PCNSL that has returned or not responded to previous treatments, and who have measurable brain lesions, might be suitable for this trial. As a Phase 3 trial, it represents the final step before FDA approval, providing patients an opportunity to access potentially effective treatments early.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken certain steroids in the 14 days before starting the study, except for specific low doses. It's best to discuss your current medications with the trial team.

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

Research shows that both tirabrutinib and the combination of rituximab and temozolomide (R-TMZ) are generally safe for patients, though some side effects may occur.

For tirabrutinib, earlier studies found it usually safe and manageable. Many patients benefited from it, and while side effects can occur, they were mostly tolerable. The research indicated that tirabrutinib worked well for many patients and was safe for long-term use.

The R-TMZ combination has also been used safely to treat brain cancer. Studies found it effective and safe for people with recurring central nervous system lymphoma. Long-term results showed that this combination could help patients live longer without the cancer worsening.

In summary, both treatments have been studied and shown to be safe, although individual experiences with side effects may differ. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for brain cancer involve chemotherapy or immunotherapy drugs like Rituximab and Temozolomide, which work by attacking cancer cells in the brain. But Tirabrutinib is different; it targets a specific enzyme known as Bruton's tyrosine kinase (BTK), which plays a role in the growth of certain cancer cells. This unique mechanism could mean more precise targeting of cancer cells, potentially leading to fewer side effects and improved outcomes for patients. Researchers are excited about Tirabrutinib because it offers a new way to tackle brain cancer, possibly providing an effective alternative to the current standard treatments.

What evidence suggests that this trial's treatments could be effective for brain cancer?

Research has shown that tirabrutinib, which participants in this trial may receive, yields promising results for treating relapsed or refractory primary central nervous system lymphoma (PCNSL). In some studies, 66.7% of patients responded to tirabrutinib, and 43.8% experienced a complete response, meaning their cancer disappeared. Another treatment option in this trial is the combination of rituximab and temozolomide. Studies suggest that this combination is also effective, with 67.4% of patients responding and 57% achieving a complete response. Both treatments have potential, but their effectiveness can vary for each person. ^{1 2 4 5 6}

Who Is on the Research Team?

Clinical Team

Principal Investigator

Deciphera Pharmaceuticals, LLC

Are You a Good Fit for This Trial?

This trial is for individuals with a confirmed diagnosis of Primary Central Nervous System Lymphoma (PCNSL) that has come back or didn't respond to previous treatment. Participants should have at least one measurable brain lesion and be in stable enough health to perform daily activities (ECOG PS 0-2). They must also have proper bone marrow, kidney, and liver function and agree to follow contraceptive guidelines.

Inclusion Criteria

I agree to follow the study's birth control rules.

I can take care of myself and am up and about more than half of the day.

My blood, kidney, and liver tests are within normal ranges.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either tirabrutinib monotherapy or rituximab and temozolomide combination therapy

24 weeks

6 cycles of 28 days each

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

What Are the Treatments Tested in This Trial?

Interventions

• Rituximab
• Temozolomide
• Tirabrutinib

Trial Overview

The study compares the effectiveness and safety of tirabrutinib alone versus a combination therapy of rituximab and temozolomide (R-TMZ) in patients with relapsed or refractory PCNSL. The goal is to see which treatment works better for this type of brain cancer.

How Is the Trial Designed?

Group I: Tirabrutinib Experimental Treatment 1 Intervention

Tirabrutinib 480 milligram (mg) orally every day (QD), as monotherapy in 28-day cycles.

Group II: Rituximab-Temozolomide (R-TMZ) Active Control 2 Interventions

Rituximab 375 milligram per square meter (mg/m2) intravenously (IV) and temozolomide 150 mg/m2/day orally, as combination therapy for Cycle 1 through 6.

Who Is Running the Clinical Trial?

Ono Pharmaceutical Co. Ltd

Lead Sponsor

Trials

182

Recruited

97,100+

Shinji Takai

Ono Pharmaceutical Co. Ltd

Chief Medical Officer since 2023

MD from an unspecified institution

Gyo Sagara

Ono Pharmaceutical Co. Ltd

Chief Executive Officer since 2024

PhD in Pharmaceutical Sciences from Kyoto University

Deciphera Pharmaceuticals, LLC

Industry Sponsor

Trials

19

Recruited

2,100+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6171986/

Long-term outcomes of rituximab, temozolomide and high ...

57% of patients achieved CR and 10.9% achieved partial response (PR) for an overall response rate (ORR) of 67.4%. The ORR in PCNSL was 81% versus 47.4% in ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3220260/

Combination Therapy with Rituximab and Temozolomide for ...

One study with 15 patients reported a 53% objective response rate and a median overall survival of 14 months with a 7 days on/7 days off schedule of TMZ ...

3.

academic.oup.com

academic.oup.com/noa/article-pdf/4/1/vdac105/45048445/vdac105.pdf

Use of rituximab, temozolomide, and radiation in recurrent and ...

Rituximab, temozolomide, and radiotherapy can be considered as an effective and safe salvage therapy for relapsed and recurrent central nervous system lymphoma.

4.

acsjournals.onlinelibrary.wiley.com

acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.20339

Immunochemotherapy with rituximab and temozolomide for ...

In conclusion, the combination of rituximab and temozolomide demonstrated efficacy against recurrent PCNSL and systemic NHL metastatic to the ...

5.

ecog-acrin.org

ecog-acrin.org/press-release-adding-the-chemotherapy-pill-temozolomide-to-radiation-therapy-improves-survival-in-adult-patients-with-glioma-a-slow-growing-type-of-brain-cancer/

Clinical trial finds that adding the chemotherapy pill ...

“We found that the 10-year survival rate was 70% with the combined treatment with temozolomide chemotherapy and radiation, compared to 47% with ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02113007

Study of High-Dose Rituximab With Temozolomide as ...

This study will evaluate the safety and efficacy of high-dose rituximab combined with temozolomide in the treatment of patients with Primary Central Nervous ...