Neoplasms

All Conditions

Symptoms and General Pathology

Blood and Lymph Conditions

Immune System Diseases

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Recurrence

Lymphoma

Melanoma

Thyroid Neoplasms

Thyroid Diseases

Pheochromocytoma

Glioma

Sarcoma

Osteosarcoma

Wilms Tumor

Medulloblastoma

Neuroblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Kidney Neoplasms

Ependymoma

Rhabdomyosarcoma

Rhabdoid Tumor

Hepatoblastoma

Histiocytosis, Langerhans-Cell

Histiocytosis

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Lymphoma, Non-Hodgkin

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Glandular and Epithelial

Disease Attributes

Neuroendocrine Tumors

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neoplasms, Connective and Soft Tissue

Neoplasms, Neuroepithelial

Endocrine System Diseases

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Paraganglioma

Lung Diseases

Lung Diseases, Interstitial

Respiratory Tract Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Lymphosarcoma

Soft Tissue Sarcoma

Germ Cells Tumors

Wilms' Tumor

Ewing Sarcoma

Langerhans Cell Histiocytosis

Neuroepithelioma

Malignant Germ Cell Tumor

Neuroendocrine Tumor

Paragangliomas 1

Antineoplastic Agents

All Drugs and Chemicals

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. Patients undergo tumor disease evaluation with PET scan, CT scan, MRI, or MIBG scintigraphy throughout the trial. Patients may undergo bone marrow aspiration or biopsy at baseline, or if there is suspicion of bone marrow metastasis, or when a complete or partial response is identified, or if there is disease progression in the marrow suspected. Patients may undergo blood specimen collections throughout the trial.

Biospecimen Collection

Bone Marrow Aspiration and Biopsy

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Radionuclide Imaging

Given PO or via nasogastric or gastric tube

Christine A Pratilas

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.

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 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. Patients undergo tumor disease evaluation with positron emission tomography (PET) scan, computed tomography (CT) scan, magnetic resonance imaging (MRI), or meta-iodobenzylguanidine (MIBG) scintigraphy throughout the trial. Patients may undergo bone marrow aspiration or biopsy at baseline, or if there is suspicion of bone marrow metastasis, or when a complete or partial response is identified, or if there is disease progression in the marrow suspected. Patients may undergo blood specimen collections throughout the trial.

After completion of study treatment, patients are followed up at 30 days, then periodically thereafter.

Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial

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

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

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.

Will explore approaches to the profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid.

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.

PFS is defined as time from the initiation of subprotocol treatment, until disease progression, recurrence, death from any cause or date of last contact.

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.

National Cancer Institute (NCI)

Spots Global Cancer Trial Database for refractory rhabdoid tumor of the kidney