A Phase 1/2 Study of the Oral TRK Inhibitor larotrectinib in Pediatric patients with Advanced Solid or Primary Central Nervous System Tumors
- Conditions
- Advanced Solid or Primary Central Nervous System Tumors1002765510029211
- Registration Number
- NL-OMON54602
- Lead Sponsor
- Bayer Consumer Care AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 3
Inclusion Criteria
1. Phase 1: 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
The Phase 1 dose escalation cohorts are closed to enrollment.
Phase 1 dose expansion: In addition to the above stated Inclusion Criteria,
patients eligible for enrollment onto this cohort must have a malignancy with a
documented NTRK gene fusion.,
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, with
documented ETV6 rearrangement (or NTRK3 rearrangement after discussion with the
Sponsor) by FISH or RT-PCR or a documented NTRK fusion by e.g. NGS.
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 with a documented NTRK gene fusion with the exception
of patients with IFS (Infantile FibroSarcoma), CMN (Congenital Mesoblastic
Nephroma tumors) or SBC (Secretory Breast Cancer), they may enroll into this
cohort with documentation of an ETV6 rearrangement by FISH or RT-PCR.
Documented NTRK fusion by NGS (Next Generation Sequencing) shall be identified
through molecular assays as routinely performed at CLIA or other
similarly-certified laboratories. If CLIA or similar certification of the
laboratory performing the molecular assay is not confirmed at the time of
consent patients may be included after discussion with the Sponsor. Patients
with NTRK-fusion positive benign tumors are also eligible.
or:
(including Expansion Phase) 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.,
2. Patients with primary CNS tumors or cerebral metastasis:
a) Must be neurologically stable based on stable neurologic exam for 7 days
prior to enrollment.
b) Must have not required increasing doses of steroids within the 7 days prior
to study entry to manage CNS symptoms
c) Phase 2 only: Imaging study must be performed within 28 days of C1D1 while
on stable dose steroid medication (if needed) for at least 7 days immediately
before the imaging study., 3. Histologic verification of malignancy at original
diagnosis or relapse, except in patients with intrinsic brain stem tumors,
optic pathway gliomas, or patients with pineal tumors and elevations of
cere
Patients meeting any of the following criteria are to be excluded from study
participation:
1. Major surgery within 14 days (2 weeks) prior to C1D1., 2. Clinically
significant active cardiovascular disease or history of myocardial infarction
within 6 months prior to C1D1; ongoing cardiomyopathy; or current prolonged QT
interval corrected for heart rate (QTc) interval >480 milliseconds., 3. Active
uncontrolled systemic bacterial, viral, or fungal infection., 4. Malabsorption
syndrome or other condition affecting oral absorption., 5. Current treatment
with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer other than
those allowed per Section 6.3.2., 6. Pregnancy or lactation., 7. Phase 2 only:
Prior progression while receiving approved or investigational tyrosine kinase
inhibitors targeting TRK, including entrectinib, crizotinib and lestaurtanib.
Patients who received a tropomyosin-related kinase (TRK) inhibitor for less
than 28 days of treatment and discontinued because of intolerance remain
eligible.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase 1:<br /><br>DLT (dose-limiting toxicity) of larotrectinib<br /><br><br /><br>Phase 2:<br /><br>total ORR (overall response rate), total confirmed response compared to the<br /><br>complete response (CR) or partial response (PR), depending on RECIST 1.1 or the<br /><br>RANO-criteria and INRC criteria.</p><br>
- Secondary Outcome Measures
Name Time Method