Various Treatments for Embryonal Tumor With Multilayered Rosettes

(PNOC031 Trial)

Recruiting at 2 trial locations

Overseen By PNOC Operations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Investigational agents

Disqualifiers: Uncontrolled illness, Allergic reactions, 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: 18-24 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines three different treatment plans to evaluate their effectiveness for children with a rare brain tumor called Embryonal Tumor With Multilayered Rosettes (ETMR). The study combines chemotherapy, including the drug Temozolomide, and radiotherapy to determine the most effective treatment approach. It involves multiple groups based on whether the tumor is fully removed or has spread. Children who have undergone surgery to remove their tumor and either show no signs of spread or have metastatic or residual disease may be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, contributing to important advancements in ETMR treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on enzyme-inducing anticonvulsants (medications for seizures), you might be excluded due to possible interactions with the study drugs.

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

Research shows that temozolomide is usually well-tolerated when treating embryonal tumors with multilayered rosettes (ETMR). Its use in other cancer treatments has established a well-understood safety profile. However, like many cancer treatments, it can cause side effects. Common side effects include nausea, fatigue, and low blood cell counts, which can increase infection risk.

Evidence suggests that starting with focused radiotherapy alongside temozolomide might be beneficial. Although this combination has shown better results, the treatment remains intense and may have serious side effects. Researchers closely monitor participants in studies to manage any side effects effectively.

Prospective trial participants should discuss the potential risks and benefits with their healthcare provider. Providers can offer advice based on individual health needs and assist in deciding if joining the trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for embryonal tumor with multilayered rosettes because they explore different combinations of chemotherapy and radiotherapy tailored to the patient's condition. Unlike traditional treatments that typically follow a one-size-fits-all approach, these investigational methods adjust the intensity and sequence of chemotherapy and radiotherapy based on whether the disease is metastatic or non-metastatic. For instance, some patients receive high-dose chemotherapy with stem cell rescue, which is a promising technique aimed at enhancing the effectiveness of the treatment while potentially minimizing long-term side effects. These personalized strategies are designed to improve outcomes by precisely targeting the tumor while considering the patient's unique needs.

What evidence suggests that this trial's treatments could be effective for Embryonal Tumor With Multilayered Rosettes?

Research has shown that the chemotherapy drug temozolomide may help treat Embryonal Tumor With Multilayered Rosettes (ETMR), a rare brain tumor. In this trial, participants in different cohorts will receive various treatment combinations. Some will receive early radiotherapy alongside standard-dose chemotherapy, while others will receive high-dose chemotherapy with the option of radiotherapy at the end. In one case, a child lived longer when treated with both radiotherapy and temozolomide compared to other treatments. Studies also suggest that starting radiotherapy early, along with temozolomide, might be more effective than using strong chemotherapy alone. While doctors continue to improve ETMR treatments, these findings indicate that temozolomide could be a useful option for managing this aggressive tumor. ^{6 7 8 9 10}

Who Is on the Research Team?

Sabine Mueller, MD, PhD, MAS

Principal Investigator

University of California, San Francisco

Derek Hanson, MD

Principal Investigator

Hackensack Meridian Health

Are You a Good Fit for This Trial?

This trial is for children with a newly diagnosed brain cancer called Embryonal Tumor With Multilayered Rosettes (ETMR). Participants must be suitable for chemotherapy, radiation therapy, and potential surgical procedures to remove the tumor. Specific eligibility criteria are not provided.

Inclusion Criteria

My cancer is confirmed to be a specific type with a certain cell pattern.

My age does not limit my participation.

For enrollment, a confirmation of a minimum of 10-20 unstained formalin-fixed paraffin-embedded (FFPE) slides or 1 block (15-20 mg) with tumor content of 40% or greater is required. Anything less must be discussed and approved by the study chairs prior to enrollment.

Exclusion Criteria

Participants who are receiving any other tumor directed investigational agents.

I have had cancer treatment other than surgery.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo surgical resection of the tumor prior to enrollment

1-2 weeks

Treatment

Participants receive induction chemotherapy and focal radiotherapy, followed by additional chemotherapy

18-24 weeks

Follow-up

Participants are monitored for survival outcomes and disease progression

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Radiotherapy
• Temozolomide

Trial Overview The study tests a treatment plan that includes induction chemotherapy to shrink the tumor, high-dose chemotherapy to target cancer cells, and focal radiation therapy aimed directly at the tumor area after surgery.

How Is the Trial Designed?

Group I: Cohort 3B: Metastatic or residual disease, high-dose chemotherapy Experimental Treatment 7 Interventions

Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 5 years.

Group II: Cohort 3A: Metastatic or residual disease, early radiotherapy Experimental Treatment 7 Interventions

Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort will receive standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 5 years.

Group III: Cohort 2: Gross-total resection, non-metastatic, high-dose chemotherapy Experimental Treatment 7 Interventions

Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 2 years.

Group IV: Cohort 1: Gross-total resection, non-metastatic, early radiotherapy Experimental Treatment 7 Interventions

Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 2 years.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Pacific Pediatric Neuro-Oncology Consortium

Collaborator

Trials

16

Recruited

840+

Solving Kids' Cancer

Collaborator

Trials

11

Recruited

200+

Pediatric Neuro-Oncology Consortium

Collaborator

Pediatric Neuro-Oncology Consortium

Collaborator

Trials

4

Recruited

130+

Published Research Related to This Trial

A study involving 16 patients with primary CNS tumors demonstrated that Dralitem® capsules of temozolomide are bioequivalent to the reference product, Temodal®, meaning they are absorbed in the body at similar rates and extents under fasting conditions.

The most common side effects reported were mild, including vomiting and abdominal pain, with no serious adverse events, indicating that Dralitem® is a safe alternative to Temodal® for treating high-grade gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-Label, Two-Way Crossover, Single-Dose Bioequivalence Study of Temozolomide 200 mg/m2 (Dralitem® vs. Temodal® Capsules) in Patients with Primary Tumors of the Central Nervous System Under Fasting Conditions. Muggeri, A., Vago, M., Pérez, S., et al.[2018]

Temozolomide (TMZ) is an effective oral treatment for malignant gliomas, providing significant survival benefits while being generally well tolerated by patients.

While most side effects of TMZ are mild to moderate, there is a risk of severe hematologic adverse events, such as myelodysplastic syndrome and aplastic anemia, which have been documented in the literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. Scaringi, C., De Sanctis, V., Minniti, G., et al.[2018]

Citations

1. redjournal.org redjournal.org/article/S0360-3016(24)02293-4/fulltext

Outcomes Following Radiation Therapy (RT) for Embryonal ... Embryonal tumor with multilayered rosettes (ETMR) represents a rare pediatric CNS embryonal tumor; limited survival estimates are around 25%.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40358803/

Outcomes following radiation therapy for embryonal tumor ... Outcomes following radiation therapy for embryonal tumor with multilayered rosettes (ETMR): results from the Pediatric Proton/Photon Consortium Registry (PPCR).

3. sciencedirect.com sciencedirect.com/science/article/pii/S0360301624022934

Outcomes Following Radiation Therapy (RT) for Embryonal ... Embryonal tumor with multilayered rosettes (ETMR) represents a rare pediatric CNS embryonal tumor; limited survival estimates are around 25%. ...

4. academic.oup.com academic.oup.com/nop/article-abstract/12/2/197/7909892

Evaluating the efficacy of radiotherapy in patients with ... The 5-year survival rate has been reported to be between 0% and 30%. Treatment of ETMR is very unstandardized and typically consists of surgical resection, ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40110061/

Evaluating the efficacy of radiotherapy in patients with ... The 5-year survival rate has been reported to be between 0% and 30%. Treatment of ETMR is very unstandardized and typically consists of surgical ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06861244

Embryonal Tumor With Multilayered Rosettes (PNOC031) Participants will be assessed for survival outcomes for up to 2 years. Follow-up procedures are to be captured under the PNOC COMP protocol. Participants will ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X24000679

Superior outcome but high incidence of ... Embryonal tumor with multilayered rosettes (ETMR) is a rare and highly aggressive embryonal brain tumor in young children. Treatment of this tumor often ...

8. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.584681/full

Potential Importance of Early Focal Radiotherapy ... ETMR is a very rare, aggressive embryonal tumor with reported survival times averaging 12 months. Because of the median age of 37 months at ...

9. researchgate.net researchgate.net/publication/347351111_ETMR-10_EARLY_FOCAL_RADIOTHERAPY_AND_TEMOZOLOMIDE_FOLLOWING_COMPLETE_RESECTION_APPEAR_SUPERIOR_TO_INTENSIVE_CHEMOTHERAPY_AND_DELAYED_RADIOTHERAPY_IN_CHILDREN_WITH_EMBRYONAL_TUMORS_WITH_MULTILAYERED_RO

etmr-10. early focal radiotherapy and temozolomide ... Embryonal tumor with multilayered rosettes (ETMR) is a rare, aggressive embryonal central nervous system tumor characterized by LIN28A ...

10. academic.oup.com academic.oup.com/neuro-oncology/article/22/Supplement_3/iii324/6018937

ETMR-08. INTERNATIONAL CONSENSUS PROTOCOL FOR ... Embryonal tumors with multilayer rosettes (ETMR) are rare and highly-aggressive central nervous system (CNS) neoplasms which occur primarily in ...