Summary

Eligibility
for people ages up to 18 years (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Amit Sabnis
Photo of Amit Sabnis
Amit Sabnis

Description

Summary

This is an open-label, Phase 1/2 multicenter dose escalation study in pediatric patients with relapsed or refractory extracranial solid tumors (Phase 1), with additional expansion cohorts (Phase 2) in patients with primary brain tumors harboring NTRK1/2/3 or ROS1 gene fusions, and extracranial solid tumors harboring NTRK1/2/3 or ROS1 gene fusions.

Official Title

A Phase 1/2, Open-Label, Dose-Escalation And Expansion Study Of Entrectinib (Rxdx-101) In Pediatrics With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options

Keywords

Solid Tumors CNS Tumors 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 Sarcoma Ewing sarcoma Glial tumors Salivary Gland Cancer (MASC) Papillary thyroid cancer Medulloblastoma Wilms tumor (anaplastic) Neoplasms Central Nervous System Neoplasms Entrectinib Extracranial solid tumors harboring NTRK1/2/3, CNS tumors harboring- NTRK1/2/3, ROS1, ALK Expansion: CNS tumors harboring NTRK1/2/3, ROS1 Expansion: Extracranial solid tumors harboring NTRK1/2/3, ROS1

Eligibility

You can join if…

Open to people ages up to 18 years

  1. Disease status:
  2. Phase 1 portion (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1
  3. Phase 2 portion:
  4. Part B: Participants must have measurable or evaluable disease, as defined by RANO
  5. Part C (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1 ± Curie Scale
  6. Part D: Participants must have measurable or evaluable disease, as defined by RECIST v1.1
  7. Part E (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1 ± Curie Scale or RANO
  8. Tumor type:
  9. Phase 1 portion:
  10. Part A: Relapsed or refractory extracranial solid tumors
  11. Phase 2 portion
  12. 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
  13. 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
  14. Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse
  15. Archival tumor tissue from diagnosis or, preferably, at relapse
  16. Performance status: Lansky or Karnofsky score ≥ 60% and minimum life expectancy of at least 4 weeks
  17. 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
  18. Participants must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment
  19. Adequate organ and neurologic function
  20. 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.
  21. . 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

You CAN'T join if...

  1. Receiving other experimental therapy
  2. Known congenital long QT syndrome
  3. History of recent (3 months) symptomatic congestive heart failure or ejection fraction ≤50% at screening
  4. Known active infections
  5. Familial or personal history of congenital bone disorders, bone metabolism alterations or osteopenia
  6. Receiving Enzyme Inducing Antiepileptic Drugs (EIAEDs) within 14 days of first dose.
  7. Prior treatment with approved or investigational TRK or ROS1 inhibitors
  8. Known hypersensitivity to entrectinib or any of the other excipients of the investigational medicinal product
  9. Patients with NB with bone marrow space-only disease
  10. . Incomplete recovery from acute effects of any surgery prior to treatment.
  11. . Active gastrointestinal disease or other malabsorption syndromes that would impact drug absorption.
  12. . 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.

Locations

  • UCSF Benioff Children's Hospital; UCSF Pediatrics Hematology Oncology accepting new patients
    San Francisco California 94158 United States
  • Children'S Hospital of Orange County completed
    Orange California 92868-3874 United States

Lead Scientist at UCSF

  • Amit Sabnis
    Assistant Professor, Pediatrics. Authored (or co-authored) 22 research publications.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Hoffmann-La Roche
ID
NCT02650401
Phase
Phase 1/2
Study Type
Interventional
Last Updated