Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
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|ClinicalTrials.gov Identifier: NCT03213704|
Recruitment Status : Recruiting
First Posted : July 11, 2017
Last Update Posted : January 17, 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 Malignant Glioma NTRK1 Fusion Positive NTRK2 Fusion Positive NTRK3 Fusion Positive Recurrent Central Nervous System Neoplasm Recurrent Childhood Ependymoma Recurrent Childhood Malignant Germ Cell Tumor Recurrent Childhood Medulloblastoma Recurrent Childhood Non-Hodgkin Lymphoma Recurrent Childhood Rhabdomyosarcoma Recurrent Childhood Soft Tissue Sarcoma Recurrent Ewing Sarcoma Recurrent Glioma Recurrent Hepatoblastoma Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Solid Neoplasm Recurrent Neuroblastoma Recurrent Osteosarcoma Recurrent Peripheral Primitive Neuroectodermal Tumor Refractory Central Nervous System Neoplasm Refractory Childhood Malignant Germ Cell Tumor Refractory Langerhans Cell Histiocytosis Refractory Malignant Solid Neoplasm Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Rhabdoid Tumor Stage III Osteosarcoma AJCC v7 Stage III Soft Tissue Sarcoma AJCC v7 Stage IV Osteosarcoma AJCC v7 Stage IV Soft Tissue Sarcoma AJCC v7 Stage IVA Osteosarcoma AJCC v7 Stage IVB Osteosarcoma AJCC v7 Wilms Tumor||Other: Laboratory Biomarker Analysis Drug: Larotrectinib Other: Pharmacological Study||Phase 2|
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with LOXO-101 (larotrectinib) with advanced solid tumors (including central nervous system [CNS] tumors), non-Hodgkin lymphomas or histiocytic disorders harboring NTRK 1/2/3 fusions.
I. To estimate the progression free survival in pediatric patients treated with LOXO-101 (larotrectinib) with advanced solid tumors (including CNS tumors), non-Hodgkin lymphomas or histiocytic disorders with NTRK 1/2/3 fusions.
II. To obtain additional information about the tolerability of LOXO-101 (larotrectinib) in children with relapsed or refractory cancer.
III. To provide preliminary estimates of the pharmacokinetics of LOXO-101 (larotrectinib) in children with relapsed or refractory cancer.
I. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
Patients receive larotrectinib orally (PO) or via nasogastric- or gastric-tube twice per day (BID) on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
|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 LOXO-101 (Larotrectinib) in Patients With Tumors Harboring Actionable NTRK Fusions|
|Actual Study Start Date :||July 24, 2017|
|Estimated Primary Completion Date :||September 30, 2024|
|Estimated Study Completion Date :||September 30, 2024|
Experimental: Treatment (larotrectinib)
Patients receive larotrectinib PO or via nasogastric- or gastric-tube BID on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Given PO or via nasogastric- or gastric-tube
Other: Pharmacological Study
- Objective response rate [ Time Frame: Up to 5 years ]Will be determined by Response Evaluation Criteria in Solid Tumors.
- Progression free survival [ Time Frame: The time from the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 5 years ]Progression free survival along with the confidence intervals will be estimated using the Kaplan-Meier method. Patients with local calls of disease progression (i.e. calls made by the treating institution), will be counted as having had an event, even if the central review does not declare progression. Progression free survival will be reported based on central radiology review as a secondary analysis, if adequate number of disagreements in progressions exist between the treating institutions and the central radiology review to make such an analysis meaningful.
- Incidence of adverse events [ Time Frame: Up to 5 years ]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 of larotrectinib [ Time Frame: Pre-dose, 1, 2, 4, and 6-8 hours after morning dose of day 1 course 1 and pre-dose of day 1 course 2 ]A descriptive analysis of pharmacokinetic parameters of LOXO-101 (larotrectinib) will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The pharmacokinetic parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). All these analyses will be descriptive and exploratory and hypotheses generating in nature.
- Ability to detect NTRK fusions in circulating cell-free tumor deoxyribonucleic acid in plasma [ Time Frame: Up to 5 years ]A descriptive analysis of the exploratory aims will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
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): NCT03213704
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|Principal Investigator:||Katherine Janeway||Children's Oncology Group|