Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
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|ClinicalTrials.gov Identifier: NCT04284774|
Recruitment Status : Recruiting
First Posted : February 26, 2020
Last Update Posted : October 27, 2020
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Adrenal Gland Pheochromocytoma Recurrent Ectomesenchymoma Recurrent Ependymoma Recurrent Ewing Sarcoma Recurrent Hepatoblastoma Recurrent Kidney Wilms Tumor Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Germ Cell Tumor Recurrent Malignant Glioma Recurrent Medulloblastoma Recurrent Melanoma Recurrent Neuroblastoma Recurrent Non-Hodgkin Lymphoma Recurrent Osteosarcoma Recurrent Peripheral Primitive Neuroectodermal Tumor Recurrent Rhabdoid Tumor Recurrent Rhabdoid Tumor of the Kidney Recurrent Rhabdomyosarcoma Recurrent Soft Tissue Sarcoma Recurrent Thyroid Gland Carcinoma Recurrent WHO Grade II Glioma Refractory Adrenal Gland Pheochromocytoma Refractory Ependymoma Refractory Ewing Sarcoma Refractory Hepatoblastoma Refractory Langerhans Cell Histiocytosis Refractory Malignant Germ Cell Tumor Refractory Malignant Glioma Refractory Medulloblastoma Refractory Melanoma Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Refractory Osteosarcoma Refractory Peripheral Primitive Neuroectodermal Tumor Refractory Rhabdoid Tumor Refractory Rhabdoid Tumor of the Kidney Refractory Rhabdomyosarcoma Refractory Soft Tissue Sarcoma Refractory Thyroid Gland Carcinoma Refractory WHO Grade II Glioma||Drug: Tipifarnib||Phase 2|
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with tipifarnib with advanced solid tumors (including central nervous system [CNS] tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in HRAS.
I. To estimate the progression free survival in pediatric patients treated with tipifarnib with advanced solid tumors (including CNS tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in HRAS.
II. To obtain information about the tolerability of tipifarnib in children and adolescents with relapsed or refractory cancer.
I. To evaluate other biomarkers as predictors of response to tipifarnib and specifically, whether tumors that harbor different missense mutations or variant allele frequency will demonstrate differential response to tipifarnib treatment.
II. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
Patients receive tipifarnib orally (PO) or via nasogastric or gastric tube twice daily (BID) on days 1-7 and 15-21. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, then periodically thereafter.
|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 Tipifarnib in Patients With Tumors Harboring HRAS Genomic Alterations|
|Actual Study Start Date :||July 13, 2020|
|Estimated Primary Completion Date :||September 30, 2027|
|Estimated Study Completion Date :||September 30, 2027|
Experimental: Treatment (tipifarnib)
Patients receive tipifarnib PO or via nasogastric or gastric tube BID on days 1-7 and 15-21. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Given PO or via nasogastric or gastric tube
- Objective response rate (complete response + partial response) in pediatric patients treated with tipifarnib [ Time Frame: From enrollment to the end of treatment, up to 2 years ]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 subprotocol treatment, until disease progression or disease recurrence or death from any cause, assessed up to 7 years ]PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
- Percentage of patients experiencing grade 3 or higher adverse events [ Time Frame: From enrollment to the end of treatment, up to 2 years ]Percentage of patients experiencing grade 3 or higher adverse events will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All patients who receive at least one dose of protocol therapy will be considered in the evaluation of toxicity.
- Biomarker analysis [ Time Frame: Up to 7 years ]Will evaluate other biomarkers as predictors of response to tipifarnib and whether tumors that harbor different missense mutations or fusions will demonstrate differential response to treatment.
- Profiling changes in tumor genomics [ Time Frame: Baseline, assessed up to 7 years ]Will explore approaches to the profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid.
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): NCT04284774
|Principal Investigator:||Christine A Pratilas||Children's Oncology Group|