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Brief Title: Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia
Official Title: Larotrectinib (LOXO-101, NSC# 788607) for Previously Untreated TRK Fusion Pediatric Solid Tumors and TRK Fusion Relapsed Pediatric Acute Leukemias
Study ID: NCT03834961
Brief Summary: This phase II trial studies the side effects and how well larotrectinib works in treating patients with previously untreated TRK fusion solid tumors and TRK fusion acute leukemia that has come back. Larotrectinib may stop the growth of cancer cells with TRK fusions by blocking the TRK enzymes needed for cell growth.
Detailed Description: PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR) of children with infantile fibrosarcoma (IFS) treated with neoadjuvant larotrectinib prior to local control. SECONDARY OBJECTIVES: I. To determine event-free survival (EFS), overall survival (OS), and duration of response (DoR) of children with IFS treated with neoadjuvant larotrectinib prior to local control. II. To determine the ORR, EFS, OS, and DoR of children with newly diagnosed TRK fusion solid tumors other than IFS treated with neoadjuvant larotrectinib prior to local control. III. To describe the toxicity of larotrectinib in children with solid tumors and acute leukemia. IV. To determine the percentage of patients with TRK fusion solid tumors with detectable circulating tumor deoxyribonucleic acid (DNA) at baseline and after 2 weeks, 4 weeks, 24 weeks of treatment, at the time of discontinuation of larotrectinib therapy, and at progression. EXPLORATORY OBJECTIVES: I. To determine the EFS, OS, and DoR of children with TRK fusion solid tumors other than IFS treated with adjuvant larotrectinib following upfront surgery with positive margins after neoadjuvant larotrectinib. II. To determine the EFS, OS, and DoR of children with TRK fusion solid tumors who experience a complete response to larotrectinib and subsequently discontinue larotrectinib therapy. III. To determine the remission induction rate for patients with recurrent/refractory TRK fusion leukemia when treated with larotrectinib. IV. To evaluate the surgical morbidity and extent of resection of initially unresectable tumors in patients with TRK fusion solid tumors who undergo surgical resection following neoadjuvant larotrectinib. V. To evaluate mechanisms of response and resistance to larotrectinib in children with TRK fusion cancers. VI. To evaluate the morphologic features of TRK fusion solid tumors at time of initial biopsy to further define criteria for pathologic diagnosis of these tumors. VII. To evaluate immunohistochemistry for pan-TRK as a screening method for TRK fusion tumors and in resection specimens following neoadjuvant treatment with larotrectinib. VIII. To evaluate the histologic response to larotrectinib in resection specimens following neoadjuvant treatment. IX. To evaluate circulating tumor DNA for the detection of the emergence of resistance mutations and recurrence in patients with TRK fusion solid tumors treated with larotrectinib. X. To evaluate the ratio of cerebrospinal fluid (CSF) to concurrent plasma concentrations of larotrectinib in patients with leukemia. XI. To evaluate the change in neurocognitive/behavioral functioning over time between baseline and 2 years post-diagnosis of patients treated on this protocol using parent-reported adaptive functioning (Adaptive Behavior Assessment System \[ABAS\]-III General Adaptive Composite), executive function (Behavior Rating Inventory of Executive Function Scales-Preschool Version \[BRIEF-P\] or BRIEF-2 Global Executive Composite Score), psychosocial functioning (Behavior Assessment System for Children \[BASC\]-3 Internalizing, Externalizing and Behavioral Symptoms Indices) and quality of life (Pediatric Quality of Life Inventory \[PedsQL\] Total score). OUTLINE: Patients receive larotrectinib orally (PO) or by nasogastric (NG) or gastric tube (G-tube) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients whose tumors shrink sufficiently while taking larotrectinib may undergo surgical resection of their tumor while on study. After completion of study treatment, patients are followed up at 3, 6, 12, 18, 24, 30, 36, and 48 months and annually thereafter for up to 5 years from the date of study entry.
Minimum Age:
Eligible Ages: CHILD, ADULT
Sex: ALL
Healthy Volunteers: No
Children's Hospital of Alabama, Birmingham, Alabama, United States
Arkansas Children's Hospital, Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center, Downey, California, United States
Children's Hospital Los Angeles, Los Angeles, California, United States
Kaiser Permanente-Oakland, Oakland, California, United States
Children's Hospital of Orange County, Orange, California, United States
UCSF Medical Center-Mission Bay, San Francisco, California, United States
Children's Hospital Colorado, Aurora, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center, Denver, Colorado, United States
Yale University, New Haven, Connecticut, United States
Alfred I duPont Hospital for Children, Wilmington, Delaware, United States
MedStar Georgetown University Hospital, Washington, District of Columbia, United States
Children's National Medical Center, Washington, District of Columbia, United States
Broward Health Medical Center, Fort Lauderdale, Florida, United States
Golisano Children's Hospital of Southwest Florida, Fort Myers, Florida, United States
University of Florida Health Science Center - Gainesville, Gainesville, Florida, United States
Nemours Children's Clinic-Jacksonville, Jacksonville, Florida, United States
Jackson Memorial Hospital-Holtz Children's Hospital, Miami, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami, Florida, United States
Nicklaus Children's Hospital, Miami, Florida, United States
Nemours Children's Hospital, Orlando, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa, Tampa, Florida, United States
Children's Healthcare of Atlanta - Egleston, Atlanta, Georgia, United States
Kapiolani Medical Center for Women and Children, Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise, Boise, Idaho, United States
Saint Jude Midwest Affiliate, Peoria, Illinois, United States
Riley Hospital for Children, Indianapolis, Indiana, United States
University of Iowa/Holden Comprehensive Cancer Center, Iowa City, Iowa, United States
Norton Children's Hospital, Louisville, Kentucky, United States
Ochsner Medical Center Jefferson, New Orleans, Louisiana, United States
Sinai Hospital of Baltimore, Baltimore, Maryland, United States
Dana-Farber Cancer Institute, Boston, Massachusetts, United States
C S Mott Children's Hospital, Ann Arbor, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health, Grand Rapids, Michigan, United States
Bronson Methodist Hospital, Kalamazoo, Michigan, United States
University of Minnesota/Masonic Cancer Center, Minneapolis, Minnesota, United States
Mayo Clinic in Rochester, Rochester, Minnesota, United States
University of Mississippi Medical Center, Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics, Kansas City, Missouri, United States
Cardinal Glennon Children's Medical Center, Saint Louis, Missouri, United States
Washington University School of Medicine, Saint Louis, Missouri, United States
Mercy Hospital Saint Louis, Saint Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha, Omaha, Nebraska, United States
University of Nebraska Medical Center, Omaha, Nebraska, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center, Lebanon, New Hampshire, United States
Hackensack University Medical Center, Hackensack, New Jersey, United States
Morristown Medical Center, Morristown, New Jersey, United States
Montefiore Medical Center - Moses Campus, Bronx, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center, New York, New York, United States
Mission Hospital, Asheville, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center, Charlotte, North Carolina, United States
Children's Hospital Medical Center of Akron, Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Cleveland Clinic Foundation, Cleveland, Ohio, United States
Nationwide Children's Hospital, Columbus, Ohio, United States
Dayton Children's Hospital, Dayton, Ohio, United States
University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
Oregon Health and Science University, Portland, Oregon, United States
Lehigh Valley Hospital-Cedar Crest, Allentown, Pennsylvania, United States
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children, Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States
Rhode Island Hospital, Providence, Rhode Island, United States
BI-LO Charities Children's Cancer Center, Greenville, South Carolina, United States
Saint Jude Children's Research Hospital, Memphis, Tennessee, United States
Dell Children's Medical Center of Central Texas, Austin, Texas, United States
Medical City Dallas Hospital, Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas, Dallas, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center, Houston, Texas, United States
University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
Primary Children's Hospital, Salt Lake City, Utah, United States
Children's Hospital of The King's Daughters, Norfolk, Virginia, United States
Seattle Children's Hospital, Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital, Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center, Tacoma, Washington, United States
University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, United States
Marshfield Medical Center-Marshfield, Marshfield, Wisconsin, United States
Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States
IWK Health Centre, Halifax, Nova Scotia, Canada
Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
Name: Theodore W Laetsch
Affiliation: Children's Oncology Group
Role: PRINCIPAL_INVESTIGATOR