Talazoparib Plus Irinotecan With or Without Temozolomide in Children With Refractory or Recurrent Solid Malignancies

Summary

The drug, talazoparib, seems to work against cancer in test tubes and animals by preventing DNA repair in damaged cells leading to their death. Investigators do not know if talazoparib combined with irinotecan will work in humans. Talazoparib has been used in only a small number of adults and children, and there is much not yet known about it.

In Arm A of this study, investigators seek to find the safest dose of irinotecan to give with talazoparib to children and young adults. In a phase I study, different dose levels of drug may be tested. The first 2 or 3 patients will be given a dose, and if none of them has a bad side-effect, the next 2 or 3 patients will be given a higher dose. No temozolomide will be given in in Arm A.

The experimental drug combination of talazoparib and irinotecan will be tested in the hopes of finding a treatment that may be effective against recurrent or refractory solid tumors. The goals of study Arm A are:

* To determine whether the combination of talazoparib and irinotecan is a beneficial treatment for your cancer;
* To learn what kind of side effects talazoparib can cause;
* To learn what kind of side effects talazoparib in combination with irinotecan can cause;
* To learn more about the biology of talazoparib in children diagnosed with solid tumors.

The purpose of Arm B is to to find the safest doses of irinotecan and temozolomide to give with talazoparib to children and young adults with a solid malignancy.. Talazoparib belongs to a family of drugs called "poly ADP ribose polymerase or PARP inhibitors." Irinotecan and temozolomide belong to a family of drugs called "DNA damaging agents."

There are two arms of this trial, A and B. In this study, investigators hope that irinotecan (administered in Arm A) and irinotecan plus temozolomide (administered in Arm B) will damage the DNA of the cancer cells. Then, talazoparib (which is a PARP inhibitor) will block the repair of the cancer cell's damaged DNA, causing the cancer cell to die (a process called "apoptosis").

There are different types of cancers found in children and young adults which appear to be vulnerable to the combination of chemotherapy agents that will be given in this study. Work carried out in the lab show that these agents may be very promising in the treatment of ewing sarcoma, germ cell tumors, wilms tumor, medulloblastoma and possibly neuroblastoma.

Conditions

• Childhood Solid Tumors

Interventions

DRUG

Talazoparib

Given orally once or twice on day 1 (depending on the dose level), then daily on days 2-6.

DRUG

Irinotecan

Given intravenously daily, days 2-6 immediately following the talazoparib dose.

DRUG

Temozolomide

Given orally daily. Dose to be determined after MTD established with talazoparib plus irinotecan.

DRUG

Filgrastim

Given subcutaneously (SubQ) once per day starting 24-36 hours after last dose of chemotherapy and continuing until post-nadir ANC is \>2,000/μL, unless peg-filgrastim is given.

DRUG

Peg-filgrastim

Given subcutaneously (SubQ) once per day starting 24-36 hours after last dose of chemotherapy and continuing until post-nadir ANC is \>2,000/μL, unless filgrastim is given.

Sponsors & Collaborators

• BioMarin Pharmaceutical

  collaborator INDUSTRY

• Alliance Pharma

  collaborator UNKNOWN

• Pfizer

  collaborator INDUSTRY

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

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

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Months

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-03-25

Primary Completion

2019-02-20

Completion

2019-08-30

FDA Drug

Yes

Countries

• United States

Study Locations