Various Treatments for Embryonal Tumor With Multilayered Rosettes

(PNOC031 Trial)

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

Trial Summary

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.

What data supports the effectiveness of the treatment Radiotherapy and Temozolomide for Embryonal Tumor With Multilayered Rosettes?

A case study showed that a child with an embryonal tumor had a good response to a combination of radiotherapy and temozolomide, which helped in longer survival. Additionally, early radiotherapy after surgery has been linked to improved survival in similar cases. ^{1 2 3 4 5}

Is temozolomide safe for humans?

Temozolomide is generally well tolerated and safe, with common side effects like fatigue, nausea, and vomiting. However, it can cause serious blood-related side effects in some cases, such as myelodysplastic syndrome (a bone marrow disorder) and aplastic anemia (a condition where the body stops producing enough new blood cells). ^{2 3 6 7 8}

How is the drug Temozolomide used for treating embryonal tumor with multilayered rosettes unique?

Temozolomide is unique in treating embryonal tumor with multilayered rosettes because it is used as part of a complex, aggressive treatment strategy that includes surgery, chemotherapy, and radiotherapy, and it has shown a good response in cases where the tumor recurs. This approach is notable because there is no standard treatment for this rare and aggressive tumor. ^{1 4 9 10 11}

What is the purpose of this trial?

This is an open-label, comprehensive, iterative investigation of evaluating the use of induction chemotherapy, high-dose chemotherapy, and focal radiation therapy in children with newly diagnosed Embryonal Tumor With Multilayered Rosettes (ETMR).

Research Team

Sabine Mueller, MD, PhD, MAS

Principal Investigator

University of California, San Francisco

Derek Hanson, MD

Principal Investigator

Hackensack Meridian Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Evaluation of the good tumor response of embryonal tumor with abundant neuropil and true rosettes (ETANTR). [2022]

2. England pubmed.ncbi.nlm.nih.gov

Treatment of embryonal tumors with multilayered rosettes with carboplatin/etoposide induction and high-dose chemotherapy within the prospective P-HIT trial. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Brief report: phase II multicenter study of temozolomide in patients with cisplatin-resistant germ cell tumors. [2018]

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

Clinicopathological characteristics and outcomes in embryonal tumor with multilayered rosettes: A decade long experience from a tertiary care centre in North India. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Importance of Early Focal Radiotherapy Following Gross Total Resection for Long-Term Survival in Children With Embryonal Tumors With Multilayered Rosettes. [2021]

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

Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. [2018]

8. New Zealand 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. [2018]

9. India pubmed.ncbi.nlm.nih.gov

Embryonal tumor with multilayered rosettes: Two case reports with a review of the literature. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience. [2022]

11. Ireland pubmed.ncbi.nlm.nih.gov

Radiation for ETMR: Literature review and case series of patients treated with proton therapy. [2022]