Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
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|ClinicalTrials.gov Identifier: NCT03213678|
Recruitment Status : Recruiting
First Posted : July 11, 2017
Last Update Posted : May 6, 2021
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm Ann Arbor Stage III Non-Hodgkin Lymphoma Ann Arbor Stage IV Non-Hodgkin Lymphoma Malignant Glioma Recurrent Ependymoma Recurrent Ewing Sarcoma Recurrent Glioma Recurrent Hepatoblastoma Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Germ Cell Tumor Recurrent Malignant Solid Neoplasm Recurrent Medulloblastoma Recurrent Neuroblastoma Recurrent Non-Hodgkin Lymphoma Recurrent Osteosarcoma Recurrent Peripheral Primitive Neuroectodermal Tumor Recurrent Primary Central Nervous System Neoplasm Recurrent Rhabdomyosarcoma Recurrent Soft Tissue Sarcoma Refractory Langerhans Cell Histiocytosis Refractory Malignant Germ Cell Tumor Refractory Malignant Solid Neoplasm Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Refractory Primary Central Nervous System Neoplasm 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 Other: Pharmacological Study Drug: Samotolisib||Phase 2|
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with samotolisib (LY3023414) with advanced solid tumors, non-Hodgkin lymphomas or central nervous system (CNS) tumors that harbor TSC loss of function mutations, that harbor other PI3K/MTOR activating mutations, and if efficacy is observed in a MATCHed cohort, in patients that lack mutations in the PI3K/MTOR pathway.
I. To estimate the progression free survival in pediatric patients treated with LY3023414 with advanced solid tumors, non-Hodgkin lymphomas or CNS tumors that harbor TSC loss of function mutations, that harbor other PI3K/MTOR activating mutations, or if efficacy is observed in a MATCHed cohort, that lack mutations in the PI3K/MTOR pathway.
II. To obtain information about the tolerability of LY3023414 in children with relapsed or refractory cancer.
III. To characterize the pharmacokinetics of LY3023414 in children with recurrent or refractory cancer.
IV. If efficacy is observed in a MATCHed cohort, to obtain preliminary information on the response rate to LY3023414 in patients that lack mutations in the PI3K/MTOR pathway.
I. To increase knowledge of the genomic landscape of relapsed pediatric solid tumors and lymphomas and identify potential predictive biomarkers (other than the genomic alteration for which study treatment was assigned) using additional genomic, transcriptomic, and proteomic testing platforms.
II. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
III. To evaluate the frequency and mechanism of biallelic loss of function, and evaluate the expression of TSC1, TSC2, and PTEN in subjects who enroll with a loss of function mutation in one of these genes.
OUTLINE: This is a dose-escalation study.
Patients receive samotolisib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unexpected toxicity.
After completion of study treatment, patients are followed up periodically.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||144 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 LY3023414 in Patients With Solid Tumors|
|Actual Study Start Date :||July 31, 2017|
|Estimated Primary Completion Date :||September 30, 2024|
|Estimated Study Completion Date :||September 30, 2024|
Experimental: Treatment (samotolisib)
Patients receive samotolisib PO BID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unexpected toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Response rate [ Time Frame: Up to 2 years ]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.
- Percentage of patients experiencing grade 3 or 4 adverse events [ Time Frame: From enrollment to the end of treatment, up to 2 years ]Will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Any eligible patient who receives at least one dose of protocol therapy will be considered in the evaluation of toxicity.
- Progression free survival (PFS) [ Time Frame: 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 2 years ]PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
- Pharmacokinetic (PK) parameters [ Time Frame: At baseline, 30 minutes, 1, 2, 4, 4, 6-8 hours, and 24 hours after the morning dose on day 1 course 1, pre-dose and at 1-2 hours after the morning dose on day 15 course 1 ]A descriptive analysis of pharmacokinetic (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).
- Potential predictive biomarker identification using additional genomic, transcriptomic, and proteomic testing platforms [ Time Frame: Up to 3 years ]A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
- Biallelic loss of function frequency and mechanism [ Time Frame: Up to 3 years ]A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
- Change in tumor genomic profile [ Time Frame: Baseline up to 3 years ]A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
- TSC1, TSC2, and PTEN expression levels [ Time Frame: Up to 3 years ]
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): NCT03213678
|Principal Investigator:||Theodore W Laetsch||Children's Oncology Group|