Summary

for people ages up to 21 years (full criteria)
at UCLA
study started
estimated completion

Description

Summary

The study is being done to test the safety of a cancer drug called larotrectinib in children. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer. The first study part (Phase 1) is done to determine what dose level of larotrectinib is safe for children, how the drug is absorbed and changed by their bodies and how well the cancer responds to the drug. The main purpose of the second study part (Phase 2) is to investigate how well and how long different cancer types respond to the treatment with larotrectininb.

Official Title

A Phase 1/2 Study of the Oral TRK Inhibitor LOXO-101 in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors

Details

The primary objectives are to determine the safety and efficacy of oral larotrectinib in pediatric patients with advanced solid or primary central nervous system (CNS) tumors.

The secondary objectives comprise e.g. the determination of the pharmacokinetic properties, the maximum tolerated dose/ recommended dose and the tumor-type specific efficacy of larotrectinib. In addition, pain status and health-related quality of life of the pediatric patients will be assessed.

Keywords

Solid Tumors Harboring NTRK Fusion Advanced solid tumors Central nervous system (CNS) tumor Extra-cranial tumor Infantile fibrosarcoma (IFS) Neurotrophic tyrosine receptor kinase (NTRK) NTRK1 NTRK2 NTRK3 Fusion Positive TRK fusion TRKA TRKB TRKC ETV6 Neoplasms Larotrectinib (Vitravki, BAY2757556) Pediatric patients_Dose 1 Pediatric patients_Dose 2 Pediatric patients_Dose 3 Pediatric patients_Dose 4 Pediatric patients_Dose 5 Pediatric patients_Dose 6 Pediatric patients_Dose 7 Pediatric patients_Recommended dose Pediatric patients_Fibrosarcoma Pediatric patients_Extracranial Pediatric patients_CNS tumors

Eligibility

You can join if…

Open to people ages up to 21 years

  • Phase 1:
  • Dose escalation: Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists; OR Infants from birth and older with a diagnosis of malignancy and with a documented NTRK fusion that has progressed or was nonresponsive to available therapies, and for which no standard or available curative therapy exists; OR Patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection. Phase I dose escalation cohorts are closed to enrollment.
  • Dose expansion: In addition to the above stated inclusion criteria, patients must have a malignancy with a documented NTRK gene fusion with the exception of patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer. Patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer may enroll into this cohort with documentation of an ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by next generation sequencing.
  • Phase 2:
  • Infants from birth and older at C1D1 with a locally advanced or metastatic infantile fibrosarcoma, patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection; OR Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists with a documented NTRK gene fusion (or in the case of infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer with documented ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by next generation sequencing) (identified through molecular assays as routinely performed at CLIA or other similarly certified laboratories). Patients with NTRK-fusion positive benign tumors are also eligible; OR Potential patients older than 21 years of age with a tumor diagnosis with histology typical of a pediatric patient and an NTRK fusion may be considered for enrollment following discussion between the local site Investigator and the Sponsor's Medical Monitor.
  • Patients with primary CNS tumors or cerebral metastasis
  • Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50.
  • Adequate hematologic function
  • Adequate hepatic and renal function

You CAN'T join if...

  • Major surgery within 14 days (2 weeks) prior to C1D1
  • Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1, ongoing cardiomyopathy; current prolonged QTc interval > 480 milliseconds
  • Active uncontrolled systemic bacterial, viral, or fungal infection
  • Current treatment with a strong CYP3A4 inhibitor or inducer. Enzyme-inducing anti-epileptic drugs (EIAEDs) and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed.
  • Phase 2 only:
  • Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK, including entrectinib, crizotinib and lestaurtanib. Patients who received a TRK inhibitor for less than 28 days of treatment and discontinued because of intolerance remain eligible.

Locations

  • UCLA Jonsson Comprehensive Cancer Center in progress, not accepting new patients
    Los Angeles California 90095 United States
  • Children's Hospital of Los Angeles in progress, not accepting new patients
    Los Angeles California 90027 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Bayer
ID
NCT02637687
Phase
Phase 1/2
Study Type
Interventional
Last Updated