Embryonal Tumor With Multilayered Rosettes

Официальное название

PNOC031: Protocol for Embryonal Tumor With Multilayered Rosettes (ETMR)

Обзор

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).

Подробное описание

PRIMARY OBJECTIVES I. To determine the six-month progression-free survival (PFS6) of participants with newly diagnosed, gross-totally resected, non-metastatic ETMR, treated using a regimen of induction chemotherapy and early focal radiotherapy (Cohort 1)

SECONDARY OBJECTIVES I. To determine the two-year progression-free survival (PFS) and overall survival (OS) of participants with newly diagnosed, gross-totally resected, non-metastatic ETMR (Cohort 1).

II. To determine the two-year progression-free survival (PFS) and overall survival (OS) of participants with newly diagnosed, gross-totally resected, non-metastatic ETMR (Cohort 2).

III. To determine the two-year progression-free survival (PFS), overall survival (OS) and objective response rate of participants with newly diagnosed, incompletely resected and/or metastatic ETMR (Cohort 3A and 3B)

EXPLORATORY OBJECTIVES:

I. To validate the utility of a liquid miRNA biomarker in blood and Cerebral spinal fluid (CSF) as a correlative marker of a participant's disease status.

II. To better define the genomic landscape of ETMR.

OUTLINE:

Participants with newly diagnosed ETMR will obtain either gross total, or sub-total resection surgery prior to enrollment. After surgery, participants will be assigned to 1 of 4 possible cohorts:

Cohorts 1 and 2: Participants with newly diagnosed, gross-totally resected, non-metastatic ETMR.

Cohorts 3A and 3B: Participants with newly diagnosed, incompletely resected and/or metastatic ETMR.

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 be followed under the Pediatric Neuro-Oncology Consortium (PNOC) COMP protocol until death or withdrawal from study.

Вмешательства

• Лучевая терапия Radiotherapy (RT)
  Undergo RT
• Препарат Chemotherapy Drug, Cancer - Physician's Choice
  One or more of the following may be assigned by the physician (physician's choice) per standard of care guidelines upon study enrollment following surgery: Cytarabine, Carboplatin, Cisplatin, Vincristine Sulfate injection (Vincristine PFS), Topotecan Hydrochloride, Dactinomycin, Thiotepa, Filgrastim, Cyclophosphamide, or Doxorubicin Hydrochloride. Not all participants will receive all possible drug regimens.
• Процедура Non-Investigational Surgical Resection
  Undergo surgery directly before study enrollment as part of planned care.
• Препарат Temozolomide
  Participants assigned to or whom receive optional RT will receive concurrent temozolomide
• Процедура Tumor Tissue Sample
  Tumor tissue will be collected for correlative studies
• Процедура Blood Sample
  Blood samples will be collected for correlative studies
• Процедура Cerebrospinal Fluid (CSF) Sample
  CSF samples will be collected for correlative studies

Первичные конечные точки

• Median Progression-free survival at 6 months (PFS6) (Cohort 1) [Срок оценки: Up to 6 months]

Вторичные конечные точки (2)

• Median Progression-free survival at 2 years progression-free survival (PFS) [Срок оценки: Up to 2 years]
• Median Overall Survival at 2 years (OS) [Срок оценки: Up to 2 years]

Критерии участия

The eligibility criteria listed below are interpreted literally and cannot be waived.

Критерии включения

• Participants must have either a molecularly or histologically confirmed embryonal tumor with multilayered rosettes.
• 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.
• Prior Therapy:

• Cohort 1 participants must not have received any prior tumor-directed therapy other than surgical resection.
• Cohort 2 and 3 participants may receive tumor-directed therapy prior to enrollment. These participants must be discussed with study chairs prior to enrollment.
• Participants must not have received prior radiation for treatment of tumor.
• Participants of any age are eligible.
• Participants should begin induction chemotherapy within 28 days of the most recent definitive surgical procedure. Participants beginning therapy beyond 28 days from surgery, will need to discuss with study chairs.
• Cohort specific eligibility

• Cohort 1: Gross-total resection, Eligible for early radiotherapy (please see age criteria below), and no evidence of metastatic disease.
• Cohort 2: Gross-total resection, high dose chemotherapy (please see age criteria below), and no evidence of metastatic disease.
• Cohort 3A: Metastatic or residual disease, and early radiotherapy.
• Cohort 3B: Metastatic or residual disease, and high dose chemotherapy.
• Radiotherapy Age Criteria (at the time of planned radiation): >12 months of age for participants with infratentorial tumor OR >15 months of age for participants with supratentorial tumor. For participants being treated on radiotherapy-containing arms, the legal parent/guardian or patient and the physician must be willing to allow the use of radiotherapy for treatment.
• Performance Score: Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants <=16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Organ Function Requirements:

• Peripheral absolute neutrophil count (ANC) > 75,000/mm3
• Platelet count > 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 72 hours prior to enrollment).
• Adequate Renal Function defined as:

a. Serum creatinine < 1.5 x upper limit normal (ULN) based on age and gender.

• Adequate Liver Function defined as:

• Total bilirubin < 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin < 3 x ULN or direct bilirubin < 1.5 x ULN,
• alanine aminotransferase (ALT) < 3 x ULN,
• aspartate aminotransferase (AST) < 3 x ULN,
• Adequate Neurologic Function defined as:

a. Participants with seizure disorder may be enrolled if well controlled. Participants on enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drugs.

• As chemotherapeutic agents used in this trial are known to be teratogenic, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of study therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Participants must be enrolled on PNOC COMP prior to enrollment on PNOC031 if PNOC COMP is open to accrual at the enrolling institution.
• A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.

Критерии исключения

• Cohort 1 only: Participants who have received any prior tumor-directed therapy other than surgical intervention
• Participants who are receiving any other tumor directed investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study.
• Uncontrolled intercurrent illness.
• Women of childbearing potential must not be pregnant or breast-feeding.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• University of Alabama at Birmingham — Birmingham
• University of California, San Francisco — San Francisco
• Riley Hospital for Children at Indiana University Health — Indianapolis
• Johns Hopkins University — Baltimore
• Washington University in St. Louis — St Louis
• Hackensack University Medical Center — Hackensack
• St. Jude Children's Research Hospital — Memphis
• University of Utah — Salt Lake City

Идентификаторы

NCT: NCT06861244 · 240830 · NCI-2025-01764

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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