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 (Vitrakvi, 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 lestaurtinib.
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