NCT02095132

Adavosertib and Irinotecan Hydrochloride in Treating Younger Patients With Relapsed or Refractory Solid Tumors

A Phase 1/2 Study of AZD1775 (MK-1775) in Combination With Oral Irinotecan in Children, Adolescents, and Young Adults With Relapsed or Refractory Solid Tumors

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 76 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of adavosertib and irinotecan hydrochloride in treating younger patients with solid tumors that have come back (relapsed) or that have not responded to standard therapy (refractory). Adavosertib and irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of adavosertib (AZD1755 \[MK-1775\]) administered on days 1 through 5 every 21 days, in combination with oral irinotecan (irinotecan hydrochloride), to children with recurrent or refractory solid tumors. II. To define and describe the toxicities of AZD1755 (MK-1775) in combination with oral irinotecan administered on this schedule. III. To characterize the pharmacokinetics of AZD1755 (MK-1775) in children with refractory cancer. SECONDARY OBJECTIVES: I. To preliminarily define the antitumor activity of AZD1755 (MK-1775) and irinotecan within the confines of a Phase 1 study. II. To obtain initial phase 2 efficacy data on the anti-tumor activity of AZD1755 (MK-1775) in combination with irinotecan administered to children with relapsed or refractory neuroblastoma, in children with relapsed or refractory medulloblastoma/CNS PNET (central nervous system primitive neuroectodermal tumor) and in children with relapsed or refractory rhabdomyosarcoma. III. To investigate checkpoint over-ride by AZD1755 (MK-1775) via the mechanism-based pharmacodynamic (PD) biomarker of decreased cyclin-dependent kinase 1 (CDK1) phosphorylation in correlative and exploratory studies. IV. To evaluate potential predictive biomarkers of AZD1755 (MK-1775) sensitivity, including v-myc avian myelocytomatosis viral oncogene homolog (MYC), v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), phosphorylated-WEE1 G2 checkpoint kinase (p-Wee1), enhancer of zeste homolog 2 (Drosophila) (EZH2) and gamma-H2A histone family, member gamma-(H2AX) in tumor tissues in correlative and exploratory studies. OUTLINE: This is a phase I, dose-escalation followed by a phase II study. Patients receive irinotecan hydrochloride orally (PO) and adavosertib PO on days 1-5. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Conditions

• Central Nervous System Embryonal Tumor With Rhabdoid Features
• Central Nervous System Embryonal Tumor, Not Otherwise Specified
• Central Nervous System Ganglioneuroblastoma
• Embryonal Tumor With Multilayered Rosettes, C19MC-Altered
• Pineoblastoma
• Primary Central Nervous System Neoplasm
• Recurrent Childhood Central Nervous System Embryonal Neoplasm
• Recurrent Malignant Solid Neoplasm
• Recurrent Medulloblastoma
• Recurrent Neuroblastoma
• Recurrent Rhabdomyosarcoma
• Refractory Malignant Solid Neoplasm
• Refractory Medulloblastoma
• Refractory Neuroblastoma
• Refractory Rhabdomyosarcoma

Interventions

Type	Name	Description
DRUG	Adavosertib	Given PO
DRUG	Irinotecan Hydrochloride	Given PO

Timeline

• Start date: 2014-03-28
• Primary completion: 2020-12-31
• Completion: 2023-06-30
• First posted: 2014-03-24
• Last updated: 2023-09-26
• Results posted: 2022-10-05

Locations

24 sites across 2 countries: United States, Canada