Onivyde + Talazoparib/Temozolomide for Ewing Sarcoma

Recruiting in Palo Alto (17 mi)

+9 other locations

Sara Federico, M.D., receives NCI award ...

Overseen bySara M Federico, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: St. Jude Children's Research Hospital

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Research Team

Sara M Federico, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for children and young adults aged between 1 and 30 with recurrent or refractory solid tumors, including Ewing sarcoma. Participants must have measurable disease, be in a certain health condition (Karnofsky >50% or Lansky >50%), have adequate organ function, not be pregnant or breastfeeding, agree to use contraception, and have recovered from previous treatments.

Inclusion Criteria

My cancer can be measured or seen on tests.

My organs and bone marrow are functioning well.

My cancer came back or didn't respond after my first treatment.

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Exclusion Criteria

I am using two forms of birth control.

I agree not to donate sperm or eggs for a specified period after taking the study drug.

Pregnant or breastfeeding

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Treatment Details

Interventions

Onivyde (Topoisomerase I inhibitor)
Talazoparib (PARP inhibitor)
Temozolomide (Alkylating agent)

Trial OverviewThe study tests Onivyde combined with either talazoparib or temozolomide in two separate arms (A & B) to find the highest tolerable doses against solid tumors. It includes expansion arms for different tumor types at these doses. Phase II focuses on Ewing sarcoma patients testing the same combinations.

Participant Groups

2Treatment groups

Active Control

Group I: (Arm A) ONI plus TALActive Control2 Interventions

The phase I/II study will evaluate a treatment regimen; nanoliposomal irinotecan (nal-IRN, Onivyde) plus talazoparib (TAL)

Group II: (Arm B) ONI plus TMZActive Control2 Interventions

The phase I/II study will evaluate a treatment regimen; Onivyde (ONI) plus temozolomide (TMZ)