NCT02392793

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

A Phase I Study of Talazoparib (BMN 673) Plus Irinotecan With or Without Temozolomide in Children With Refractory or Recurrent Solid Malignancies

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 12 Months – 25 Years
• Healthy volunteers: Not accepted

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.

Detailed description

In Arm A of this study, talazoparib will be administered orally on day 1 either once or twice per day depending on the dose level of the enrolled participant. Both oral talazoparib and intravenous (IV) irinotecan will then be administered daily, on days 2-6. Each cycle will last 21 days. Once the maximum tolerated doses (MTDs) for talazoparib and irinotecan are determined, a second arm of the study (Arm B) will open administering talazoparib, irinotecan and temozolomide. Talazoparib will be given orally, on days 1-6. Intravenous irinotecan and oral temozolomide will be given on days 2-6. The study will estimate the maximum tolerated doses, describe the toxicities of therapy, estimate the response rate and characterize the pharmacokinetics of the combined talazoparib plus irinotecan with or without temozolomide. This study is a traditional dose escalation study using a standard 3+3 phase I design. In Arm A, six or more dose levels will be evaluated for the combination of talazoparib and irinotecan. Once the MTDs of Arm A are determined, Arm B will open and evaluate the combination of talazoparib, irinotecan and temozolomide. PRIMARY OBJECTIVES - ARM A * To estimate the maximum tolerated doses (MTDs) of talazoparib (daily, days 1-6) combined with irinotecan (daily, days 2-6) given every 21 days in children with refractory or recurrent solid malignancies. * To identify and describe the dose limiting toxicities of talazoparib and irinotecan administered in combination to patients with refractory or recurrent solid malignancies. PRIMARY OBJECTIVES - ARM B * To estimate the maximum tolerated dose (MTD) of temozolomide (given daily, days 2-6) when combined with talazoparib (daily, days 1-6) and irinotecan (daily, days 2-6) given every 21 days in children with refractory or recurrent solid malignancies. * To identify and describe the dose limiting toxicities of temozolomide, talazoparib and irinotecan administered in combination to patients with refractory or recurrent solid malignancies. SECONDARY OBJECTIVES * To estimate the response rate, within the confines of a phase I study, to talazoparib plus irinotecan and talazoparib plus irinotecan and temozolomide administered in combination in pediatric patients with refractory or recurrent solid malignancies. * To characterize the pharmacokinetics of talazoparib plus irinotecan and talazoparib plus irinotecan and temozolomide when given in combination to children with refractory or recurrent solid malignancies.

Conditions

• Childhood Solid Tumors

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2015-03-25
• Primary completion: 2019-02-20
• Completion: 2019-08-30
• First posted: 2015-03-19
• Last updated: 2021-02-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study