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

May 23, 2026 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00926
        • University Pediatric Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Providence Alaska Medical Center
    • Arizona
      • Mesa, Arizona, United States, 85202
        • Banner Children's at Desert
      • Phoenix, Arizona, United States, 85016
        • Phoenix Childrens Hospital
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
    • Arkansas
      • Little Rock, Arkansas, United States, 72202-3591
        • Arkansas Children's Hospital
    • California
      • Downey, California, United States, 90242
        • Kaiser Permanente Downey Medical Center
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Loma Linda, California, United States, 92354
        • Loma Linda University Medical Center
      • Long Beach, California, United States, 90806
        • Miller Children's and Women's Hospital Long Beach
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Los Angeles, California, United States, 90095
        • Mattel Children's Hospital UCLA
      • Madera, California, United States, 93636
        • Valley Children's Hospital
      • Oakland, California, United States, 94609
        • UCSF Benioff Children's Hospital Oakland
      • Oakland, California, United States, 94611
        • Kaiser Permanente-Oakland
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital Stanford University
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • San Diego, California, United States, 92123
        • Rady Children's Hospital - San Diego
      • San Diego, California, United States, 92134
        • Naval Medical Center -San Diego
      • San Francisco, California, United States, 94158
        • UCSF Medical Center-Mission Bay
      • Torrance, California, United States, 90502
        • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Medical Center
      • New Haven, Connecticut, United States, 06520
        • Yale University
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I duPont Hospital for Children
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Children's National Medical Center
      • Washington D.C., District of Columbia, United States, 20007
        • MedStar Georgetown University Hospital
    • Florida
      • Fort Lauderdale, Florida, United States, 33316
        • Broward Health Medical Center
      • Fort Myers, Florida, United States, 33908
        • Golisano Children's Hospital of Southwest Florida
      • Gainesville, Florida, United States, 32610
        • UF Health Cancer Institute - Gainesville
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic-Jacksonville
      • Miami, Florida, United States, 33155
        • Nicklaus Children's Hospital
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital
      • Orlando, Florida, United States, 32803
        • AdventHealth Orlando
      • Orlando, Florida, United States, 32806
        • Arnold Palmer Hospital for Children
      • Pensacola, Florida, United States, 32504
        • Sacred Heart Hospital
      • St. Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital
      • Tampa, Florida, United States, 33607
        • Saint Joseph's Hospital/Children's Hospital-Tampa
      • West Palm Beach, Florida, United States, 33407
        • Saint Mary's Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Children's Healthcare of Atlanta - Arthur M Blank Hospital
      • Savannah, Georgia, United States, 31404
        • Memorial Health University Medical Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
    • Idaho
      • Boise, Idaho, United States, 83712
        • Saint Luke's Cancer Institute - Boise
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Chicago, Illinois, United States, 60611
        • Lurie Children's Hospital-Chicago
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Peoria, Illinois, United States, 61637
        • OSF Children's Hospital of Illinois
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
      • Indianapolis, Indiana, United States, 46260
        • Ascension Saint Vincent Indianapolis Hospital
    • Iowa
      • Des Moines, Iowa, United States, 50309
        • Blank Children's Hospital
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
      • Louisville, Kentucky, United States, 40202
        • Norton Children's Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center Jefferson
      • New Orleans, Louisiana, United States, 70118
        • Children's Hospital New Orleans
    • Maine
      • Bangor, Maine, United States, 04401
        • Eastern Maine Medical Center
      • Scarborough, Maine, United States, 04074
        • Maine Children's Cancer Program
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center - University Campus
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • C S Mott Children's Hospital
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • East Lansing, Michigan, United States, 48823
        • Michigan State University
      • Grand Rapids, Michigan, United States, 49503
        • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Royal Oak, Michigan, United States, 48073
        • Corewell Health Children's
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota/Masonic Cancer Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospitals and Clinics
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • St Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • St Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
      • Omaha, Nebraska, United States, 68114
        • Children's Hospital and Medical Center of Omaha
    • Nevada
      • Las Vegas, Nevada, United States, 89144
        • Summerlin Hospital Medical Center
      • Las Vegas, Nevada, United States, 89109
        • Sunrise Hospital and Medical Center
      • Las Vegas, Nevada, United States, 89135
        • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
      • Las Vegas, Nevada, United States, 89102
        • University Medical Center of Southern Nevada
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Morristown, New Jersey, United States, 07960
        • Morristown Medical Center
      • New Brunswick, New Jersey, United States, 08901
        • Saint Peter's University Hospital
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical Center
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Mineola, New York, United States, 11501
        • NYU Langone Hospital - Long Island
      • New Hyde Park, New York, United States, 11040
        • The Steven and Alexandra Cohen Children's Medical Center of New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • New York, New York, United States, 10065
        • NYP/Weill Cornell Medical Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Medical Center
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Asheville, North Carolina, United States, 28801
        • Mission Hospital
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Charlotte, North Carolina, United States, 28204
        • Novant Health Presbyterian Medical Center
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Greenville, North Carolina, United States, 27834
        • East Carolina University
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
    • Ohio
      • Akron, Ohio, United States, 44308
        • Children's Hospital Medical Center of Akron
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Childrens Hospital
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
      • Dayton, Ohio, United States, 45404
        • Dayton Children's Hospital
      • Toledo, Ohio, United States, 43606
        • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Children's Hospital
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital-Cedar Crest
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Philadelphia, Pennsylvania, United States, 19134
        • Saint Christopher's Hospital for Children
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Prisma Health Richland Hospital
      • Greenville, South Carolina, United States, 29605
        • BI-LO Charities Children's Cancer Center
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • T C Thompson Children's Hospital
      • Knoxville, Tennessee, United States, 37916
        • East Tennessee Childrens Hospital
      • Memphis, Tennessee, United States, 38105
        • Saint Jude Children's Research Hospital
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
      • Nashville, Tennessee, United States, 37203
        • The Children's Hospital at TriStar Centennial
    • Texas
      • Austin, Texas, United States, 78723
        • Dell Children's Medical Center of Central Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • El Paso, Texas, United States, 79905
        • El Paso Children's Hospital
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • Lubbock, Texas, United States, 79410
        • Covenant Children's Hospital
      • Lubbock, Texas, United States, 79415
        • UMC Cancer Center / UMC Health System
      • San Antonio, Texas, United States, 78207
        • Children's Hospital of San Antonio
      • San Antonio, Texas, United States, 78229
        • Methodist Children's Hospital of South Texas
      • Temple, Texas, United States, 76508
        • Scott and White Memorial Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Hospital
    • Vermont
      • Burlington, Vermont, United States, 05405
        • University of Vermont and State Agricultural College
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
      • Norfolk, Virginia, United States, 23507
        • Children's Hospital of The King's Daughters
      • Portsmouth, Virginia, United States, 23708-2197
        • Naval Medical Center - Portsmouth
      • Richmond, Virginia, United States, 23298
        • VCU Massey Comprehensive Cancer Center
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
      • Spokane, Washington, United States, 99204
        • Providence Sacred Heart Medical Center and Children's Hospital
      • Tacoma, Washington, United States, 98405
        • Mary Bridge Children's Hospital and Health Center
      • Tacoma, Washington, United States, 98431
        • Madigan Army Medical Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University Healthcare
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center - University Hospital
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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
      • Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately

    • Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive

      • >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
    • Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
    • Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
    • Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
    • Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator
    • Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)

    • Stem cell infusions (with or without total body irradiation [TBI]):

      • Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
      • Autologous stem cell infusion including boost infusion: >= 42 days
    • Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)

    • Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation

      • Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
    • Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radio-pharmaceutical therapy
    • Patients must not have received prior exposure to tipifarnib

  • For patients with solid tumors without known bone marrow involvement (within 7 days prior to enrollment):

    • Peripheral absolute neutrophil count (ANC) >= 1000/mm^3

  • For patients with solid tumors without known bone marrow involvement (within 7 days prior to enrollment):

    • Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment) or

  • A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):

    • Age: Maximum serum creatinine (mg/dL)

      • 1 to < 2 years: male (0.6), female (0.6)
      • 2 to < 6 years: male (0.8), female (0.8)
      • 6 to < 10 years: male (1), female (1)
      • 10 to < 13 years: male (1.2), female (1.2)
      • 13 to < 16 years: male (1.5), female (1.4)
      • >= 16 years: male (1.7), female (1.4)
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. (For the purpose of this study, the ULN for SGPT is 45 U/L.) (within 7 days prior to enrollment)
  • Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
  • Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0) resulting from prior therapy must be =< grade 2
  • Patients must be able to swallow intact tablets or crushed tablets mixed in water, orange juice, apple juice, tomato juice, ginger ale, applesauce, yogurt, protein shake, or a dietary supplement drink (such as Ensure). Percutaneous endoscopic gastrostomy (PEG)-tube or nasogastric tube administration is permitted
  • All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines

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
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Tipifarnib
Tipifarnib tablets
Other Names:
  • R115777
  • Zarnestra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 2 years from study entry

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients Experiencing Grade 3 or Higher Adverse Events
Time Frame: Up to 2 years from study entry
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
Up to 2 years from study entry
Progression Free Survival (PFS)
Time Frame: Up to 6 months from study entry
The Kaplan-Meier method will be used to estimate the 6-month PFS. PFS is defined as time from initiation of protocol treatment to disease progression, recurrence, death from any cause, or date of last contact
Up to 6 months from study entry

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 7 years
Profiling Changes in Tumor Genomics
Time Frame: Baseline, prior to cycle 5, end of treatment, assessed up to 7 years
Will explore approaches to the profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid.
Baseline, prior to cycle 5, end of treatment, assessed up to 7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Christine A Pratilas, Children's Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 13, 2020

Primary Completion (Actual)

March 31, 2024

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

February 25, 2020

First Submitted That Met QC Criteria

February 25, 2020

First Posted (Actual)

February 26, 2020

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 23, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2020-01015 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180886 (U.S. NIH Grant/Contract)
  • APEC1621M (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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