Talazoparib Plus Irinotecan With or Without Temozolomide in Children With Refractory or Recurrent Solid Malignancies
Status:
Completed
Trial end date:
2019-08-30
Target enrollment:
Participant gender:
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.