Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
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|ClinicalTrials.gov Identifier: NCT03233204|
Recruitment Status : Recruiting
First Posted : July 28, 2017
Last Update Posted : August 16, 2019
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma Deleterious ATM Gene Mutation Deleterious BRCA1 Gene Mutation Deleterious BRCA2 Gene Mutation Deleterious RAD51C Gene Mutation Deleterious RAD51D Gene Mutation Histiocytosis Low Grade Glioma Malignant Glioma Recurrent Childhood Central Nervous System Neoplasm Recurrent Childhood Ependymoma Recurrent Childhood Malignant Germ Cell Tumor Recurrent Childhood Non-Hodgkin Lymphoma Recurrent Childhood Rhabdomyosarcoma Recurrent Childhood Soft Tissue Sarcoma Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Recurrent Glioma Recurrent Hepatoblastoma Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Solid Neoplasm Recurrent Medulloblastoma Recurrent Neuroblastoma Recurrent Osteosarcoma Refractory Central Nervous System Neoplasm Refractory Childhood Malignant Germ Cell Tumor Refractory Ependymoma Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Refractory Glioma Refractory Hepatoblastoma Refractory Langerhans Cell Histiocytosis Refractory Malignant Glioma Refractory Malignant Solid Neoplasm Refractory Medulloblastoma Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Refractory Osteosarcoma Refractory Rhabdomyosarcoma Refractory Soft Tissue Sarcoma Rhabdoid Tumor Wilms Tumor||Drug: Olaparib||Phase 2|
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with olaparib with advanced solid tumors (including central nervous system [CNS] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in the deleterious genetic alterations in the DNA damage repair (DDR) pathway.
I. To estimate the progression free survival in pediatric patients treated with olaparib with advanced solid tumors including non-Hodgkin lymphomas, CNS tumors, and histiocytosis that harbor deleterious genetic alterations in the DDR pathway.
II. To obtain information about the tolerability of olaparib in children and adolescents with relapsed or refractory cancer.
III. To provide preliminary estimates of the pharmacokinetics of olaparib in children and adolescents with relapsed or refractory cancer.
I. To explore approaches to profiling changes in tumor genomics over time through the evaluation of circulating tumor DNA.
Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||49 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)- Phase 2 Subprotocol of Olaparib in Patients With Tumors Harboring Defects in DNA Damage Repair Genes|
|Actual Study Start Date :||July 24, 2017|
|Estimated Primary Completion Date :||September 30, 2024|
|Estimated Study Completion Date :||September 30, 2024|
Experimental: Treatment (olaparib)
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
- Objective response rate (complete response/partial response) [ Time Frame: Up to 4 years ]Determined using Response Evaluation Criteria in Solid Tumors version 1.1. A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method.
- Progression free survival (PFS) [ Time Frame: From the initiation of protocol treatment to the occurrence of disease progression, disease recurrence, or death from any cause, assessed up to 4 years ]PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
- Incidence of toxicity [ Time Frame: Up to 4 years ]Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.
- Pharmacokinetics (PK) of olaparib [ Time Frame: Pre-dose on day 1, and pre-dose, 1, 2, 4, and 6-8 hours after morning dose on day 8 of cycle 1 ]A descriptive analysis of PK parameters 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).
- Change in tumor genomic profile [ Time Frame: Cycle 5 day 1 to 4 years ]Approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid will be explored. Descriptive analysis will be performed and will be summarized with simple summary statistics.
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): NCT03233204
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|Principal Investigator:||Julia Glade-Bender||Children's Oncology Group|