Tazemetostat for Solid Cancers and Lymphoma

No longer recruiting at 127 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inducers/inhibitors

Disqualifiers: Pregnancy, Uncontrolled infection, Myeloid malignancies, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well tazemetostat works for individuals with specific types of brain tumors, solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have either recurred or are unresponsive to treatment. Tazemetostat aims to halt cancer cell growth by blocking a protein called EZH2, crucial for cancer cell proliferation. The trial seeks participants with specific gene mutations and measurable tumors, particularly those who have not succeeded with other treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a promising therapy.

Do I have to stop taking my current medications to join the trial?

The trial requires that you stop taking certain medications before joining. You cannot be on other anti-cancer agents, investigational drugs, or strong inducers or inhibitors of CYP3A4. If you're on corticosteroids, you need to be on a stable or decreasing dose for at least 7 days before enrolling.

Is there any evidence suggesting that tazemetostat is likely to be safe for humans?

Research has shown that tazemetostat has been tested for safety in patients with various types of cancer. In earlier studies, most participants tolerated tazemetostat well, though some experienced serious side effects. For example, in one study involving patients with solid tumors, seven individuals died due to treatment-related issues.

Despite these serious cases, the FDA has approved tazemetostat for other conditions, such as follicular lymphoma, indicating it is considered safe for certain uses. Ongoing studies continue to assess its safety and effectiveness in different types of cancer. It is crucial to discuss potential risks and benefits with a doctor when considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tazemetostat is unique because it targets a specific protein called EZH2, which plays a role in cancer cell growth. Unlike conventional treatments for solid cancers and lymphoma, such as chemotherapy and radiation, which attack rapidly dividing cells in general, tazemetostat specifically inhibits this protein, potentially leading to fewer side effects. Researchers are excited because this targeted approach could be more effective for patients who have cancers driven by EZH2 mutations, offering a more personalized treatment option.

What evidence suggests that tazemetostat might be an effective treatment for solid cancers and lymphoma?

Studies have shown that tazemetostat can help treat certain cancers. In patients with lymphoma, 38% experienced tumor reduction or disappearance. Tazemetostat blocks a protein called EZH2, which is linked to cancer growth, potentially stopping tumors from growing, especially those with specific gene changes. The treatment is generally well-tolerated, with manageable side effects. Early results are promising, but larger studies are needed to confirm its effectiveness for different cancer types. Participants in this trial will receive tazemetostat as part of the study treatment. ^{2 6 7 8 9}

Who Is on the Research Team?

Susan N Chi

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for patients with relapsed or refractory advanced solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with specific gene mutations (EZH2, SMARCB1, SMARCA4). Participants must have measurable disease and recovered from previous cancer therapies. They need adequate blood counts and organ function and can't have had prior EZH2 inhibitor treatment.

Inclusion Criteria

My cancer can be seen and measured on scans, or if I have neuroblastoma, it shows up on special scans even if not measurable.

My blood counts meet the required levels and I haven't needed platelet transfusions in the last week.

My kidney function is normal or near normal.

Exclusion Criteria

My blood tests do not show signs of specific blood disorders.

I do not have any infections that are currently uncontrolled.

Pregnant or breast-feeding women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tazemetostat orally twice daily on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Tazemetostat

Trial Overview The trial tests Tazemetostat's effectiveness in stopping tumor growth by blocking a protein called EZH2. It targets patients whose cancers haven't responded to other treatments and who carry certain genetic mutations that may be affected by this drug.

How Is the Trial Designed?

Group I: Treatment (tazemetostat) Experimental Treatment 1 Intervention

Patients receive tazemetostat PO BID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Tazemetostat is already approved in United States, European Union for the following indications:

Approved in United States as Tazverik for:

• Epithelioid sarcoma
• Follicular lymphoma

Approved in European Union as Tazverik for:

• Epithelioid sarcoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Children's Oncology Group

Collaborator

Trials

467

Recruited

241,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8955562/

Tazemetostat: EZH2 Inhibitor - PMC Clinical outcomes found that 38% of lymphoma patients had an objective response rate (ORR), with median time to first response being 3.5 months. The median ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01897571

NCT01897571 | Study of Tazemetostat as Single Agent in ... This is an open-label, multicenter, Phase 1/2 study of tazemetostat as a single agent in subjects with advanced solid tumors or with B-cell lymphomas.

3. aacrjournals.org aacrjournals.org/mct/article/24/10_Supplement/C017/766215/Abstract-C017-Preclinical-evaluation-of-EZH2

Abstract C017: Preclinical evaluation of EZH2 inhibitor ... Tazemetostat showed synergistic anti-tumor effects and increased apoptosis induction with PI3Kδ inhibitor amdizalisib in B and T-cell lymphomas.

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/211723Orig1s000MultidisciplineR.pdf

Multi-Discipline Review - accessdata.fda.gov The clinical pharmacology data are supportive of the efficacy results. The primary evidence of effectiveness at the proposed 800 mg BID ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00331-1/fulltext

Efficacy and safety of tazemetostat, an EZH2 inhibitor, in ... Results with tazemetostat indicated a manageable safety profile, with no noticeable safety signals. Larger trials are needed. The clinical outcomes of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9892962/

EZH2 inhibition by tazemetostat: mechanisms of action, safety ... Of note, in the Phase I study, including a majority of patients with solid tumors, seven patients died with a TEAE (four patients with general status ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/213400s000lbl.pdf

TAZVERIK (tazemetostat) - accessdata.fda.gov The major efficacy outcome measures were confirmed overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8427481/

Tazemetostat for patients with relapsed or refractory follicular ... We investigated the activity and safety of tazemetostat, a first-in-class, oral EZH2 inhibitor, in patients with follicular lymphoma.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05023655?term=tazemetostat&viewType=Table&rank=6

Phase II Study of Tazemetostat in Solid Tumors Harboring ... The FDA approved targeted agent tazemetostat inhibits EZH2 and induces durable tumor responses in patients with B-cell non-Hodgkin's lymphoma and ...