Study of Onivyde With Talazoparib or Temozolomide in Children With Recurrent Solid Tumors and Ewing Sarcoma

Summary

The phase I portion of this study is designed for children or adolescents and young adults (AYA) with a diagnosis of a solid tumor that has recurred (come back after treatment) or is refractory (never completely went away). The trial will test 2 combinations of therapy and participants will be randomly assigned to either Arm A or Arm B. The purpose of the phase I study is to determine the highest tolerable doses of the combinations of treatment given in each Arm.

In Arm A, children and AYAs with recurrent or refractory solid tumors will receive 2 medications called Onivyde and talazoparib. Onivyde works by damaging the DNA of the cancer cell and talazoparib works by blocking the repair of the DNA once the cancer cell is damaged. By damaging the tumor DNA and blocking the repair, the cancer cells may die. In Arm B, children and AYAs with recurrent or refractory solid tumors will receive 2 medications called Onivyde and temozolomide. Both of these medications work by damaging the DNA of the cancer call which may cause the tumor(s) to die.

Once the highest doses are reached in Arm A and Arm B, then "expansion Arms" will open. An expansion arm treats more children and AYAs with recurrent or refractory solid tumors at the highest doses achieved in the phase I study. The goal of the expansion arms is to see if the tumors go away in children and AYAs with recurrent or refractory solid tumors. There will be 3 "expansion Arms". In Arm A1, children and AYAs with recurrent or refractory solid tumors (excluding Ewing sarcoma) will receive Onivyde and talazoparib. In Arm A2, children and AYAs with recurrent or refractory solid tumors, whose tumors have a problem with repairing DNA (identified by their doctor), will receive Onivyde and talazoparib. In Arm B1, children and AYAs with recurrent or refractory solid tumors (excluding Ewing sarcoma) will receive Onivyde and temozolomide.

Once the highest doses of medications used in Arm A and Arm B are determined, then a phase II study will open for children or young adults with Ewing sarcoma that has recurred or is refractory following treatment received after the initial diagnosis. The trial will test the same 2 combinations of therapy in Arm A and Arm B. In the phase II, a participant with Ewing sarcoma will be randomly assigned to receive the treatment given on either Arm A or Arm B.

Conditions

• Recurrent Solid Tumor
• Recurrent Ewing Sarcoma
• Recurrent Hepatoblastoma
• Recurrent Malignant Germ Cell Tumor
• Recurrent Malignant Solid Neoplasm
• Recurrent Neuroblastoma
• Recurrent Osteosarcoma
• Recurrent Peripheral Primitive Neuroectodermal Tumor
• Recurrent Rhabdoid Tumor
• Recurrent Rhabdomyosarcoma
• Recurrent Soft Tissue Sarcoma
• Recurrent Wilms Tumor
• Refractory Ewing Sarcoma
• Refractory Hepatoblastoma
• Refractory Malignant Germ Cell Tumor
• Refractory Malignant Solid Neoplasm
• Refractory Neuroblastoma
• Refractory Osteosarcoma
• Refractory Peripheral Primitive Neuroectodermal Tumor
• Refractory Rhabdoid Tumor
• Refractory Rhabdomyosarcoma
• Refractory Soft Tissue Sarcoma

Interventions

DRUG

Onivyde

Given intravenous on Days 1 and 8

DRUG

Talazoparib

Given orally twice on Day 1 (daily maximum is 1000mcg/day), then daily on Days 2-6

DRUG

Temozolomide

Given once a day on Days 1-5.

Sponsors & Collaborators

• Pfizer

  collaborator INDUSTRY

• Ipsen

  collaborator INDUSTRY

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Sara Federico, MD · St. Jude Children's Research Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Months

Max Age

30 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-06-09

Primary Completion

2026-12-31

Completion

2026-12-31

FDA Drug

Yes

Countries

• United States
• Canada

Study Locations