A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
Start Date
3/12/2020
Completion Date
9/30/2027
Summary
Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D). Phase 2 will determine the anti-tumor activity of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring ROS1 or NTRK1-3 alterations.
Detailed Description
Enrollment of subjects into Phase 1 will proceed concurrently by age as follows: * Subjects \<12 years old will initially be enrolled in the Phase 1 part to determine the pediatric RP2D for this age group; once the pediatric RP2D is determined, subjects age \<12 years old may be enrolled into the Phase 2 part of the study. * Subjects 12 to 25 years old will be directly enrolled into the Phase 2 part concurrent with Phase 1 enrollment. Phase 1: Approximately 12 pediatric subjects with locally advanced or metastatic solid tumors, including a primary central nervous system (CNS) tumor, or anaplastic large cell lymphoma (ALCL), with disease progression or who are non-responsive or intolerant to available therapies and for which no standard or available curative therapy exists. Phase 2: Subjects will be enrolled in one of 3 cohorts as follows: Cohort 1: approximately 10-20 subjects with solid tumors characterized by NTRK fusion, TRK tyrosine kinase inhibitor (TKI)-naïve, and centrally confirmed measurable disease at baseline. Cohort 2: approximately 23 subjects with solid tumors characterized by NTRK fusion, TRK TKI-pretreated, and centrally confirmed measurable disease at baseline. Cohort 3: approximately 20 subjects with solid tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease not otherwise eligible for Cohort 1 or 2. As of the current protocol amendment, only patients with ROS1 alterations will be enrolled to this cohort.
Eligibility Criteria
Age Range: No minimum to 25 years
Interventions
Oral repotrectinib (TPX-0005)
Conditions
Locations
Children's Hospital Los Angeles
Los Angeles, California 90027-6062
United States
University of California at Los Angeles
Los Angeles, California 90095
United States
Children's Hospital Colorado - Anschutz Medical Campus
Aurora, Colorado 80045
United States
Local Institution - 2105
Orlando, Florida 32806
United States
Local Institution - 2120
Orlando, Florida 32827
United States
Children's Healthcare of Atlanta - Egleston Hospital
Atlanta, Georgia 30329
United States
Maine Medical Center
Scarborough, Maine 04074
United States
Dana Farber Cancer Institute.
Boston, Massachusetts 02215
United States
Washington University School of Medicine in St. Louis
St Louis, Missouri 63110
United States
Local Institution - 2110
New Brunswick, New Jersey 08901
United States
Local Institution - 2102
New York, New York 10065
United States
Levine Children's Hospital- Pediatric Neuro-Oncology
Charlotte, North Carolina 28203
United States
Local Institution - 2112
Cleveland, Ohio 44195
United States
Local Institution - 2114
Hershey, Pennsylvania 17033
United States
Children's Hospital of Philadelphia-Center for Childhood Cancer Research
Philadelphia, Pennsylvania 19104
United States
St. Jude Children's Research Hospital
Memphis, Tennessee 38015
United States
The University of Texas Southwestern Medical Center - Harold C Simmons Comprehensive Cancer Center
Dallas, Texas 75390
United States
Baylor College of Medicine
Houston, Texas 77030
United States
Local Institution - 2104
Houston, Texas 77030
United States
Children's Hospital of Richmond at VCU
Richmond, Virginia 23219
United States
Local Institution - 6104
Randwick, New South Wales 2031
Australia
Local Institution - 6103
Westmead, New South Wales 0
Australia
Children's Health Queensland Hospital and Health Service
South Brisbane, Queensland 4101
Australia
Perth Childrens Hospital
Nedlands, Western Australia 6009
Australia
University Of Calgary
Calgary, Alberta T3B 6A8
Canada
Stollery Children'S Hospital
Edmonton, Alberta T6G 2B7
Canada
Children'S Hospital Of Eastern Ontario
Ottawa, Ontario K1H 8L1
Canada
St Justine Hospital
Montreal, Quebec H3T 1C5
Canada
Rigshospitalet - Glostrup
Copenhagen, 2100
Denmark
Local Institution - 6111
Lyon, Rhone 69008
France
Centre Hospitalier Universitaire D'Angers
Angers, 49933
France
Centre Hospitalier Universitaire de Bordeaux - Groupe Hospitalier Pellegrin
Bordeaux, 33076
France
Institut d Hematologie et d Oncologie Pediatriques
Lyon, 69373
France
Hôpitaux Universitaires de Marseille Timone
Marseille, 13385
France
Local Institution - 6110
Marseille, 13385
France
Local Institution - 6112
Nantes, 44093
France
Local Institution - 6109
Paris, 75005
France
Institut Gustave-Roussy
Villejuif, 94805
France
Local Institution - 6108
Villejuif, 94805
France
Fondazione IRCCS - Istituto Nazionale dei Tumori
Milan, 20133
Italy
Local Institution - 6113
Padova, 35128
Italy
Local Institution - 4302
Rome, 00165
Italy
Local Institution - 6114
Torino, 10126
Italy
National University Hospital
Singapore, 119228
Singapore
KK Women's and Children's Hospital
Singapore, 229899
Singapore
Local Institution - 6303
Seoul, Seodaemun-gu 03722
South Korea
Seoul National University Hospital
Seoul, 03080
South Korea
Asan Medical Center
Seoul, 05505
South Korea
Local Institution - 6304
Seoul, 06351
South Korea
Hospital Sant Joan De Deu
Esplugues de Llobregat, Barcelona 08950
Spain
Clínica Universidad de navarra
Pamplona, Navarre 31008
Spain
Local Institution - 6105
Barcelona, 08014
Spain
Hospital Universitari Vall d'Hebron
Barcelona, 8035
Spain
Hospital Infantil Universitario Nino Jesus
Madrid, 28009
Spain
Local Institution - 6106
Madrid, 28009
Spain
Clinica Universidad de Navarra
Madrid, 28022
Spain
HM Sanchinarro University Hospital
Madrid, 28050
Spain
Hospital Universitario Virgen del Rocio
Seville, 41013
Spain
Hospital Universitario Y Politecnico La Fe
Valencia, 46026
Spain
Local Institution - 6107
Valencia, 46026
Spain
National Taiwan University Hospital
Taipei, 100225
Taiwan
Taipei Medical University Hospital
Taipei, 11031
Taiwan
Alder Hey Children's NHS Foundation Trust
Liverpool, England L12 2AP
United Kingdom
Local Institution - 4403
Birmingham, B4 6DH
United Kingdom
University Hospital of Wales
Cardiff, CF14 4XW
United Kingdom
Royal Hosp. for Children
Glasgow, G51 4TF
United Kingdom
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
United Kingdom
Great Ormond Street Hospital For Children NHS Foundation Trust
London, WC1N 3JH
United Kingdom