Talazoparib and Temozolomide in Treating Younger Patients With Refractory or Recurrent Malignancies
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|ClinicalTrials.gov Identifier: NCT02116777|
Recruitment Status : Completed
First Posted : April 17, 2014
Last Update Posted : January 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Neoplasm Childhood Solid Neoplasm Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Central Nervous System Neoplasm Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Recurrent Malignant Solid Neoplasm Refractory Central Nervous System Neoplasm||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Talazoparib Drug: Temozolomide||Phase 1 Phase 2|
I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of temozolomide when combined with a dose of talazoparib (BMN 673) given once daily for 5 days after a one day dose of BMN 673 administered orally (either once daily or twice daily), every 28 days to children with refractory or recurrent solid tumors. (Phase I) II. To define and describe the toxicities of BMN 673 given with temozolomide administered on this schedule. (Phase I) III. To characterize the pharmacokinetics of BMN 673 and temozolomide when given in combination to children with refractory or recurrent cancer. (Phase I) IV. To define the antitumor activity of BMN 673 when given with temozolomide in recurrent/refractory Ewing sarcoma and recurrent acute lymphoblastic leukemia (ALL). (Phase II)
I. To preliminarily define the antitumor activity of BMN 673 and temozolomide in pediatric patients with recurrent or refractory solid tumors within the confines of a phase I study.
II. To explore possible predictive biomarkers in archival tumor tissue from Ewing sarcoma patients in Phase II.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive talazoparib orally (PO) once daily (QD) or twice daily (BID) on days 1-6 and temozolomide PO QD on days 2-6. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2 Study of BMN 673, an Oral Poly(ADP-Ribose) Polymerase Inhibitor, Plus Temozolomide in Children With Refractory or Recurrent Malignancies|
|Actual Study Start Date :||May 16, 2014|
|Actual Primary Completion Date :||December 31, 2018|
|Actual Study Completion Date :||December 31, 2018|
Experimental: Treatment (talazoparib, temozolomide)
Patients receive talazoparib PO QD or BID on days 1-6 and temozolomide PO QD on days 2-6. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- MTD of talazoparib and temozolomide, defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicities (Phase I Part A1) [ Time Frame: 28 days ]In addition to determination of the MTD or RP2D, a descriptive summary of all toxicities will be reported.
- Objective response in patients with Ewing sarcoma or peripheral PNET assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 and criteria for CNS tumors (Phase I Part A2) [ Time Frame: Up to 24 months ]All disease responses will be reported descriptively.
- Pharmacokinetic (PK) parameters of talazoparib (Phase I Part A) [ Time Frame: Pre-dose, 1, 2, 4, 8, and 24 hours on day 1 and on day 5 or 6 of course 1 ]A descriptive analysis will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
- Best response of disease to talazoparib plus temozolomide in Ewing sarcoma or peripheral PNET patients determined according to RECIST v1.1 (Phase II Parts B and C) [ Time Frame: From the start of the treatment until disease progression/recurrence, assessed up to 24 months ]
- Best response of disease to talazoparib plus temozolomide in patients with ALL using the leukemia rating scale and peripheral blood counts (Phase II Parts B and C) [ Time Frame: From the start of the treatment until disease progression/recurrence, assessed up to 24 months ]
- Incidence of toxicities, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 (Phase II Parts B and C) [ Time Frame: Up to 30 days ]Described separately.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02116777
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|Principal Investigator:||Eric Schafer||COG Phase I Consortium|