Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options (STARTRK-NG)
Solid Tumors, CNS Tumors
About this trial
This is an interventional treatment trial for Solid Tumors focused on measuring TRK, Tyrosine kinase, NTRK, NTRK1, NTRK2, NTRK3, ROS1, ALK, Pediatric, Relapsed, Refractory, Solid Tumor, Metastatic Cancer, Gene rearrangement, Neuroblastoma, Infantile fibrosarcoma, Secretory breast cancer, Congenital mesoblastic nephroma, Pontine glioma, Brain tumors, CNS tumors, Sarcoma, Ewing sarcoma, Glial tumors, Salivary Gland Cancer (MASC), Papillary thyroid cancer, Medulloblastoma, Wilms tumor (anaplastic)
Eligibility Criteria
Inclusion Criteria:
Disease status:
- Phase 1 portion (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1
Phase 2 portion:
- Part B: Participants must have measurable or evaluable disease, as defined by RANO
- Part C (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1 ± Curie Scale
- Part D: Participants must have measurable or evaluable disease, as defined by RECIST v1.1
- Part E (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1 ± Curie Scale or RANO
Tumor type:
Phase 1 portion:
* Part A: Relapsed or refractory extracranial solid tumors
Phase 2 portion
- Part B: Primary brain tumors with NTRK1/2/3 or ROS1 gene fusions; gene fusions are defined as those predicted to translate into a fusion protein with a functional TRKA/B/C or ROS1 kinase domain, without a concomitant second oncodriver as determined by a nucleic acid-based diagnostic testing method
- Part D: Extracranial solid tumors (including NB) with NTRK1/2/3 or ROS1 gene fusions; gene fusions are defined as those predicted to translate into a fusion protein with a functional TRKA/B/C or ROS1 kinase domain, without a concomitant second oncodriver as determined by a nucleic acid-based diagnostic testing method
- Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse
- Archival tumor tissue from diagnosis or, preferably, at relapse
- Performance status: Lansky or Karnofsky score ≥ 60% and minimum life expectancy of at least 4 weeks
- Prior therapy: Participants must have a disease that is locally advanced, metastatic, or where surgical resection is likely to result in severe morbidity, and who have no satisfactory treatment options for solid tumors and primary CNS tumors that are neurotrophic tyrosine receptor kinase (NTRK) or ROS1 fusion-positive
- Participants must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment
- Adequate organ and neurologic function
- Females of childbearing potential must have a negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation. Agreement to remain abstinent or use use combined contraceptive methods prior to study entry, for the duration of study participation and in the following 90 days after discontinuation of study treatment.
- For male participants with a female partner of childbearing potential or a pregnant female partner: Agreement to remain abstinent or use a condom during the treatment period and for at least 3 months after the last dose of study drug
Exclusion Criteria:
- Receiving other experimental therapy
- Known congenital long QT syndrome
- History of recent (3 months) symptomatic congestive heart failure or ejection fraction ≤50% at screening
- Known active infections
- Familial or personal history of congenital bone disorders, bone metabolism alterations or osteopenia
- Receiving Enzyme Inducing Antiepileptic Drugs (EIAEDs) within 14 days of first dose.
- Prior treatment with approved or investigational TRK or ROS1 inhibitors
- Known hypersensitivity to entrectinib or any of the other excipients of the investigational medicinal product
- Patients with NB with bone marrow space-only disease
- Incomplete recovery from acute effects of any surgery prior to treatment.
- Active gastrointestinal disease or other malabsorption syndromes that would impact drug absorption.
- Other severe acute or chronic medical or psychiatric condition or lab abnormality that may increase the risk associated with study participation, drug administration or may interfere with the interpretation of study results.
Sites / Locations
- Children'S Hospital of Orange County
- Rady Childrens Hospital
- UCSF Benioff Children's Hospital; UCSF Pediatrics Hematology Oncology
- Children's Hospital Colorado; Center For Cancer/Blood Disorder
- Children's National Medical Center; Department of Pediatrics
- Egleston Children's Hospital at Emory University Atlanta; Pediatric Hematology/Oncology
- University of Chicago; Comer Children's Hospital/Department of Pediatrics
- Johns Hopkins University
- Dana Farber Cancer Institute
- University of Minnesota Childrens' Hospital
- Washington University,St. Louis Children's Hospital; Neurology, Movement Disorder
- Morgan Stanley Children's Hospital; Herbert Irving Cancer Center
- Memorial Sloan Kettering Cancer Center; Pediatrics
- Cincinnati Children's Hospital Medical Center
- Nationwide Children's Hospital; Dept. of Pulmonology
- Oregon Health & Science Uni
- Children's Hospital of Philadelphia
- St. Jude Children'S Research Hospital
- Cook Childrens Medical Center
- Texas Children's Cancer and Hematology Center
- Primary Children's Hospital
- The Hospital for Sick Children
- Beijing Children's Hospital, Capital Medical University; Oncological Surgery Department
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
- Centre Leon Berard; Pediatrie
- Hôpital de la Timone, Oncologie Pédiatrique
- Hopital Purpan; Pediatrie - Hematologie - Oncologie pediatrique
- Institut Gustave Roussy; Service de Pathologie Morphologique
- Universitaetsklinikum Heidelberg
- Hong Kong Children's Hospital
- Fondazione IRCCS Istituto Nazionale dei Tumori; Struttura Complessa di Pediatria Oncologica
- A. O. Città della Salute e della Scienza di Torino; SC Oncoematologia e Centro Trapianti AOOIRM
- Seoul National University Hospital
- Hospital Sant Joan de Deu; Servicio de Oncologia y Hematologia
- Hospital Infantil Universitario Nino Jesus
- National Taiwan University Hospital; Department of Paediatrics
- Chang Gung Memorial Hospital, Linkou; Department of Pediatric Internal Medicine
- Leeds General Infirmary
- Royal Victoria Infirmary; Pharmacy
- Royal Marsden NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Extracranial solid tumors harboring NTRK1/2/3,
CNS tumors harboring- NTRK1/2/3, ROS1, ALK
Neuroblastoma
Non-neuroblastoma, extracranial solid tumors
Any participant unable to swallow capsules
Expansion: CNS tumors harboring NTRK1/2/3, ROS1
Expansion: Extracranial solid tumors harboring NTRK1/2/3, ROS1
Arm closed for further enrollment ROS1, ALK non-gene fusion molecular alterations Oral entrectinib (RXDX-101)
Arm closed for further enrollment molecular alterations, including gene fusions Oral entrectinib (RXDX-101)
Arm closed for further enrollment Oral entrectinib (RXDX-101)
Arm closed for further enrollment harboring - NTRK1/2/3, ROS1, ALK gene fusions Oral entrectinib (RXDX-101)
Arm closed for further enrollment Any participant who otherwise meet all other eligibility criteria Oral entrectinib (RXDX-101)
gene fusions Oral entrectinib (RXDX-101)
NTRK 1,2,3 and ROS1 fusions Oral entrectinib (RXDX-101)