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

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Trial ID: NCT02637687

Purpose

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 Larotrectinib in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors

Stanford Investigator(s)

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. 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 lestaurtinib.
      Patients who received a TRK inhibitor for less than 28 days of treatment and
      discontinued because of intolerance remain eligible.

Intervention(s):

drug: Larotrectinib (Vitrakvi, BAY2757556)

Recruiting

I'm Interested

Contact Information

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

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