Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial

March 5, 2024 updated by: National Cancer Institute (NCI)

NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of LOXO-292 in Patients With Tumors Harboring RET Gene Alterations

This phase II pediatric MATCH treatment trial studies how well selpercatinib works in treating patients with solid tumors that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), lymphomas, or histiocytic disorders that have activating RET gene alterations. Selpercatinib may block the growth of cancer cells that have specific genetic changes in an important signaling pathway (called the RET pathway) 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 selpercatinib (LOXO-292) with advanced solid tumors (including central nervous system [CNS] tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in the RET pathway.

SECONDARY OBJECTIVES:

I. To estimate the progression free survival in pediatric patients treated with selpercatinib (LOXO-292) with advanced solid tumors (including CNS tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in the RET pathway.

II. To obtain information about the tolerability of selpercatinib (LOXO-292) in children and adolescents with relapsed or refractory cancer.

EXPLORATORY OBJECTIVE:

I. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).

OUTLINE:

Patients receive selpercatinib orally (PO) twice daily (BID) on days 1-28 on study. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.

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

Study Type

Interventional

Enrollment (Estimated)

49

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

  • Australia
    • Western Australia
      • Perth, Western Australia, Australia, 6009
        • Perth Children's Hospital
  • 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, 90027
        • Children's Hospital Los Angeles
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
      • 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, District of Columbia, United States, 20010
        • Children's National Medical Center
      • Washington, 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
        • University of Florida Health Science Center - 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
      • Saint 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 Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta - Egleston
      • 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
        • Saint Jude Midwest Affiliate
      • 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, 48824
        • Michigan State University Clinical Center
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Royal Oak, Michigan, United States, 48073
        • Beaumont Children's Hospital-Royal Oak
    • 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
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospitals and Clinics
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • Saint 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
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Mineola, New York, United States, 11501
        • NYU Winthrop Hospital
      • 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
      • 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, 78229
        • University of Texas Health Science Center at San Antonio
      • 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
        • Virginia Commonwealth University/Massey 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
      • 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 and must have been given a treatment assignment to MATCH to APEC1621N based on the presence of an actionable mutation
  • Patients must be >= 12 months and =< 21 years of age at the time of study 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 MRI or 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 [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 radiopharmaceutical therapy
    • Patients must not have received prior exposure to selpercatinib (LOXO-292) or other specific RET inhibitors

  • 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. (within 7 days prior to enrollment) (For the purpose of this study, the ULN for SGPT is 45 U/L.)
  • Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
  • Corrected QT (QTc) interval =< 480 milliseconds (within 7 days prior to enrollment)
  • 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 (2) highly effective contraceptive method for the duration of study treatment and for at least 2 weeks after the last dose of selpercatinib (LOXO-292). Male study participants are to refrain from sperm donation during treatment and for 2 weeks after the last dose of selpercatinib (LOXO-292)
  • 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 moderate or strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
  • Proton pump inhibitors (PPIs), H2 receptor antagonists and antacids: Concomitant use of PPIs during selpercatinib (LOXO-292) therapy should be avoided if feasible. If co-administration of selpercatinib and PPI is necessary, administer selpercatinib with a meal. If H2 receptor antagonist is necessary, administer selpercatinib 2 hours before or 10 hours after H2 receptor antagonist administration. If antacid use is necessary, administer selpercatinib 2 or more hours before or 2 or more hours after antacid administration
  • Patients who have major surgery within 14 days prior to cycle 1 day 1 (C1D1) are not eligible. (Central line placement or subcutaneous port placement is not considered major surgery)
  • Patients with known clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of selpercatinib (LOXO-292) are excluded
  • Patients with known hypersensitivity to any of the components of the investigational agent, LOXO 292 are excluded
  • Patients with uncontrolled hypertension are excluded
  • Patients with uncontrolled symptomatic hyperthyroidism and hypothyroidism (i.e. the patient required a modification to current thyroid medication in 7 days prior to enrollment) are excluded
  • Patients with uncontrolled symptomatic hypercalcemia and hypocalcemia are excluded
  • 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 (selpercatinib)
Patients receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
Procedure: Computed Tomography
Undergo CT, PET/CT, and/or CT/MRI
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Procedure: Magnetic Resonance Imaging
Undergo MRI, PET/MRI, and/or CT/MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Positron Emission Tomography
Undergo PET, PET/CT, and/or PET/MRI
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
Procedure: Radionuclide Imaging
Undergo scintigraphy
Other Names:
  • NM
  • Nuclear Medicine
  • nuclear medicine scan
  • radioimaging
  • Radionuclide Scanning
  • Scan
  • Scintigraphy
Drug: Selpercatinib
Given PO
Other Names:
  • LOXO-292
  • RET Kinase Inhibitor LOXO-292
  • Retevmo
  • WHO 10967
  • Retsevmo
Procedure: X-Ray Imaging
Undergo x-ray imaging
Other Names:
  • Conventional X-Ray
  • Diagnostic Radiology
  • Medical Imaging, X-Ray
  • Radiographic Imaging
  • Radiography
  • RG
  • Static X-Ray
  • X-Ray
  • Plain film radiographs
  • Radiographic imaging procedure (procedure)

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 selpercatinib (LOXO-292)
Time Frame: Up to 2 years
Will be determined by Response Evaluation Criteria in Solid Tumors. 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.
Up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: From the initiation of subprotocol (APEC1621N) 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.
From the initiation of subprotocol (APEC1621N) 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
Percentage of patients experiencing grade 3 or 4 adverse events
Time Frame: Up to 2 years
Evaluated by Common Terminology Criteria for Adverse Events version 5. Any eligible patient who receives at least one dose of protocol therapy will be considered in the evaluation of toxicity.
Up to 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Profiling changes in tumor genomics
Time Frame: Up to time of disease progression or end of protocol therapy
Will explore approaches to the profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid. A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
Up to time of disease progression or end of protocol therapy

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Collaborators

Children's Oncology Group

Investigators

  • Principal Investigator: Andrea T Franson, 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)

May 3, 2021

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

March 24, 2020

First Submitted That Met QC Criteria

March 24, 2020

First Posted (Actual)

March 25, 2020

Study Record Updates

Last Update Posted (Actual)

March 6, 2024

Last Update Submitted That Met QC Criteria

March 5, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2020-01756 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180886 (U.S. NIH Grant/Contract)
  • APEC1621N (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

product manufactured in and exported from the U.S.

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.

Clinical Trials on Refractory Lymphoma

Clinical Trials on Computed Tomography

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Papua New Guinea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe