Trial of NLG802 Indoximod Prodrug Plus Temozolomide for Patients With Progressive Pediatric Brain Cancer

Официальное название

Phase 1b Trial of NLG802 Indoximod Prodrug Plus Temozolomide for Patients With Progressive Pediatric Brain Cancer

Обзор

This is a open label Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of escalating oral doses of NLG802, an investigational agent intended to inhibit the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, in combination with temozolomide chemotherapy in children with primary brain tumors.

Подробное описание

The study will enroll subjects 5 to 21 years of age with relapsed or refractory primary brain or spinal malignancy of any histology, who have exhausted available curative treatment options. A standard 3+3 dose-escalation design will be used to determine the pediatric maximum tolerated dose (MTD) for NLG802 indoximod prodrug in combination with temozolomide (Treatment Regimen). The MTD of NLG802 for the Treatment Regimen will be the highest dose level where no more than 1 of 6 subjects have (a) Regimen-Limiting Toxicity(/ies) (RLT\[s\]) in Cycle 1, which will be 28 days duration plus any toxicity-related delay before starting Cycle 2. Toxicity will be defined and graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. All subjects will have timed blood draws for NLG802 pharmacokinetic (PK) analysis in Cycle 1.

Вмешательства

• Препарат NLG802 (indoximod Prodrug)
  NLG802 will be taken by mouth twice daily, throughout each treatment cycle.
• Препарат Temozolomide
  Temozolomide will be taken by mouth once daily, on days 1-5 of each treatment cycle.

Первичные конечные точки

• Maximum tolerated dose in pediatric participants for NLG802 in combination with temozolomide. [Срок оценки: Cycle 1, which will be 28 days duration plus any toxicity-related delay before starting Cycle 2.]

Вторичные конечные точки (5)

• Incidence of Regimen-limiting toxicities in in pediatric participants for NLG802 in combination with temozolomide. [Срок оценки: Cycle 1, which will be 28 days duration plus any toxicity-related delay before starting Cycle 2.]
• Pharmacokinetics in pediatric participants for NLG802 in combination with temozolomide [Срок оценки: Cycle 1, which will be 28 days duration plus any toxicity-related delay before starting Cycle 2.]
• Overall survival for NLG802 in combination with temozolomide. [Срок оценки: Day 1 up to 12 months.]
• Evidence of efficacy for NLG802 in combination with temozolomide based on change to objective response rate. [Срок оценки: Day 1 up to 12 months.]
• Percentage of patients with adverse events [Срок оценки: Day 1 up to 12 months.]

Критерии участия

Критерии включения

• Age must be ≥ 5 years and < 22 years.
• Subjects must have relapsed or treatment-refractory primary brain or spinal malignancy of any histology.
• Subjects are allowed to have surgical debulking and/or radiation/proton therapy prior to enrollment in this trial.
• Tumor tissue is required for central review of tissue diagnosis and biomarker correlate studies.
• Collection of baseline blood samples for required biomarker correlate trials.
• Performance score: Lansky or Karnofsky performance status score must be ≥ 70.
• Life expectancy must be ≥ 3 months.
• Hemoglobin ≥ 10 g/dL
• Platelets ≥ 100,000/μL
• ANC ≥ 1,000/μL
• ALT ≤ 3-times upper limit of normal.
• Total bilirubin ≤ 1.5-times upper limit of normal.
• Adequate renal function
• Seizure disorders must be well controlled with antiepileptic medication.
• Subjects must be able to swallow pills.
• Corticosteroid therapy: When necessary for adrenal replacement, subjects may receive hydrocortisone ≤ 1.7 mg/kg/day, maximum dose 70 mg/day (or equivalent).
• At the time of starting protocol therapy, subjects must be ≥ 21 days from the administration of any prior cytotoxic therapy (including chemotherapy).
• At the time of starting protocol therapy, subjects must be ≥ 28 days from any radiation or proton therapy.
• At the time of starting protocol therapy, subjects must be ≥ 28 days from administration of antibody-based immune checkpoint-inhibitor therapies, tumor-directed vaccines, or cellular immune therapies.
• At the time of starting protocol therapy, subjects must be ≥ 56 days from administration of tumor-directed therapies using infectious agents.
• At the time of starting protocol therapy, subjects must be ≥ 90 days from a stem cell transplant with growth-factor independent recovery of adequate bone marrow function.
• Subjects, or their parent for subjects < 18 years of age, must sign an Informed Consent Form (ICF) indicating that they understand the purpose of the trial and procedures required, including biomarkers, and are willing to participate in the trial.

Критерии исключения

• Unable to swallow capsules.
• Active therapy for radiation necrosis.
• Baseline QTcB of > 470 msec at screening, and subjects with known congenital long QT syndrome.
• Clinically significant cardiovascular disease.
• Active systemic infection requiring treatment.
• Active autoimmune disease that requires systemic therapy.
• Any known bleeding diathesis.
• Subjects who are breastfeeding or pregnant women.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Augusta University, Georgia Cancer Center — Augusta

Идентификаторы

NCT: NCT07732413 · NLG8022

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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