Trial Search Results

A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children

The purpose of this study is to examine the safety and effectiveness of larotrectinib (LOXO-101) in pediatric patients with an advanced cancer harboring a fusion involving NTRK1, NTRK2, or NTRK3 (collective referred to as NTRK fusions). In Phase 1 of the study, increasing doses of larotrectinib will be tested to determine the recommended safe dose in children. In Phase 1 Dose Expansion and Phase 2, subjects will receive multiple cycles of larotrectinib to evaluate its efficacy in treating cancer. All participants must either have infantile fibrosarcoma or a documented NTRK fusion mutation.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Bayer

Stanford Investigator(s):

Intervention(s):

  • Drug: Larotrectinib (Vitravki, BAY2757556)

Phase:

Phase 1/Phase 2

Eligibility


Inclusion Criteria:

   - Phase 1 (Closed):

      - 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 (or NTRK3 rearrangement after discussion with the sponsor) 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.

   - 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

Exclusion Criteria:

   - 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.

Ages Eligible for Study

N/A - 21 Years

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Christina Baggott
650-497-7659
Recruiting