NCT02975882

Nanoparticle Albumin-Bound Rapamycin, Temozolomide, and Irinotecan Hydrochloride in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors

A Phase 1 Study of ABI-009 (NAB-RAPAMYCIN) in Pediatric Patients With Recurrent or Refractory Solid Tumors, Including CNS Tumors as a Single Agent and in Combination With Temozolomide and Irinotecan

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 33 (actual)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 12 Months – 21 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of nanoparticle albumin-bound rapamycin when given together with temozolomide and irinotecan hydrochloride in treating pediatric patients with solid tumors that have come back after treatment and a period of time during which the tumor could not be detected or has not responded to treatment. Nanoparticle albumin-bound rapamycin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nanoparticle albumin-bound rapamycin, temozolomide, and irinotecan hydrochloride may cause the cancer to stop growing or shrink for a period of time and may lessen the symptoms that are caused by the cancer.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of nanoparticle albumin-bound rapamycin (ABI-009) administered as an intravenous infusion over 30 minutes on days 1 and 8 of a 21-day cycle, in combination with temozolomide and irinotecan hydrochloride (irinotecan) (administered on days 1-5) in pediatric patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors. II. To define and describe the toxicities of single-agent ABI-009 administered as an intravenous infusion over 30 minutes on days 1 and 8 of a 21-day cycle in pediatric patients with recurrent or refractory solid tumors, including CNS tumors. III. To define and describe the toxicities of ABI-009 administered as an intravenous infusion over 30 minutes on days 1 and 8 of a 21-day cycle in combination with temozolomide and irinotecan (administered on days 1-5) in pediatric patients with recurrent or refractory solid tumors, including CNS tumors. IV. To characterize the pharmacokinetics of ABI-009 in pediatric patients with recurrent or refractory solid tumors, including CNS tumors. SECONDARY OBJECTIVE: I. To preliminarily define the antitumor activity of ABI-009 in combination with temozolomide and irinotecan within the confines of a phase 1 study. EXPLORATORY OBJECTIVE: I. To assess the biologic activity of ABI-009 by examining S6K1 and 4E-BP1 expression status in archival tumor tissue from solid tumor pediatric patients using immunohistochemistry. OUTLINE: This is a dose-escalation study of nanoparticle albumin-bound rapamycin. Patients receive nanoparticle albumin-bound rapamycin intravenously (IV) over 30 minutes on days 1 and 8 beginning on cycle 1. Patients also receive temozolomide orally (PO) and irinotecan hydrochloride PO on days 1-5 beginning on cycle 2. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Conditions

• Childhood Solid Neoplasm
• Recurrent Malignant Solid Neoplasm
• Recurrent Primary Central Nervous System Neoplasm
• Refractory Malignant Solid Neoplasm
• Refractory Primary Central Nervous System Neoplasm

Interventions

Type	Name	Description
DRUG	Irinotecan Hydrochloride	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DRUG	Sirolimus Albumin-bound Nanoparticles	Given IV
DRUG	Temozolomide	Given PO

Timeline

• Start date: 2017-08-15
• Primary completion: 2022-03-31
• Completion: 2024-12-31
• First posted: 2016-11-29
• Last updated: 2025-01-14
• Results posted: 2023-03-30

Locations

21 sites across 1 country: United States

Regulatory

• FDA-regulated drug study