NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)- Phase 2 Subprotocol of Tipifarnib in Patients With Tumors Harboring HRAS Genomic Alterations

National Cancer Institute (NCI)172 sites in 1 country5 target enrollmentOctober 13, 2020

ConditionsMalignant Solid Neoplasm 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 2 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 2 Glioma

InterventionsTipifarnib

DrugsTipifarnib

Overview

Phase: Phase 2
Intervention: Tipifarnib
Conditions: Malignant Solid Neoplasm
Sponsor: National Cancer Institute (NCI)
Enrollment: 5
Locations: 172
Primary Endpoint: Objective Response Rate (Complete Response + Partial Response) in Pediatric Patients Treated With Tipifarnib
Status: Active, not recruiting
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This phase II pediatric MATCH trial studies how well tipifarnib works in treating patients with solid tumors that have recurred or spread to other places in the body (advanced), lymphoma, or histiocytic disorders, that have a genetic alteration in the gene HRAS. Tipifarnib may block the growth of cancer cells that have specific genetic changes in a gene called HRAS and may reduce tumor size.

Detailed Description

PRIMARY OBJECTIVE: 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. SECONDARY OBJECTIVES: 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. EXPLORATORY OBJECTIVES: 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). OUTLINE: Patients receive tipifarnib tablets 350 mg/m\^2/dose orally (PO) or via nasogastric or gastric tube twice daily (BID) (maximum 600 mg/dose BID) with food 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.

Registry

clinicaltrials.gov

Start Date

October 13, 2020

End Date

September 30, 2027

Last Updated

4 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

National Cancer Institute (NCI)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patient must have enrolled onto APEC1621SC (NCT03155620) and must have been given a treatment assignment to MATCH to APEC1621M based on the presence of an actionable mutation as defined in APEC1621SC
•Patients must be \>=12 months and =\< 21 years of age at the time of study enrollment
•Patients must have a body surface area \>= 0.29 m\^2 at enrollment
•Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible. Measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
•Note: The following do not qualify as measurable disease:
•Malignant fluid collections (e.g., ascites, pleural effusions)
•Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
•Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography \[PET\] scans) except as noted for neuroblastoma
•Elevated tumor markers in plasma or cerebral spinal fluid (CSF)
•Previously radiated lesions that have not demonstrated clear progression post radiation

Exclusion Criteria

•Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective contraceptive methods for the duration of study treatment. Both female subjects and male subjects with female partners of child-bearing potential must agree to use a highly effective method of contraception for 2 weeks prior to protocol therapy, during, and at least 4 weeks after last dose of tipifarnib. In addition, since tipifarnib could induce toxicity of male reproductive organs and cause impairment of fertility, sperm cryopreservation should be recommended for male subjects wishing to preserve their fertility following tipifarnib treatment
•Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
•Patients who are currently receiving another investigational drug are not eligible
•Patients who are currently receiving other anti-cancer agents are not eligible
•Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
•Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4/5 or UGT are not eligible. Strong inducers or inhibitors of CYP3A4/5 or UGT should be avoided from 14 days prior to the 1st dose of tipifarnib to the end of the study. In addition, patients receiving agents that are sensitive or narrow therapeutic range substrates of CYP3A4/5 are not eligible. Note: CYP3A4/5 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
•Patients with known hypersensitivity to tipifarnib or any components of the tablet are not eligible
•Patients with hypersensitivity to imidazoles, such as clotrimazole, ketoconazole, miconazole and others in this drug class are not eligible
•Patients who have an uncontrolled infection are not eligible
•Patients who have received a prior solid organ transplantation are not eligible

Arms & Interventions

Treatment (tipifarnib)

Patients receive tipifarnib tablets 350 mg/m\^2/dose PO or via nasogastric or gastric tube BID (maximum 600 mg/dose BID) with food 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.

Intervention: Tipifarnib

Outcomes

Primary Outcomes

Objective Response Rate (Complete Response + Partial Response) in Pediatric Patients Treated With Tipifarnib

Time Frame: Up to 2 years from study entry

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. The revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to determine response and progression in this study, with specific criteria outlined for the different subtypes of tumors (e.g., 2-dimensional measurements for central nervous system (CNS) tumors.

Secondary Outcomes

Progression Free Survival (PFS)(Up to 6 months from study entry)
Percentage of Patients Experiencing Grade 3 or Higher Adverse Events(Up to 2 years from study entry)