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



Status:Recruiting
Conditions:Cancer, Brain Cancer, Brain Cancer, Neurology
Therapuetic Areas:Neurology, Oncology
Healthy:No
Age Range:Any - 21
Updated:4/6/2019
Start Date:December 16, 2015
End Date:September 30, 2020
Contact:Bayer Clinical Trials Contact
Email:clinical-trials-contact@bayer.com
Phone:(+)1-888-84 22937

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

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.

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.

Inclusion Criteria:

- 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

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.
We found this trial at
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sites
Los Angeles, California 90095
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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4650 Sunset Blvd
Los Angeles, California 90027
 (323) 660-2450
Principal Investigator: Leo Mascarenhas, MD
Childrens Hospital Los Angeles Children's Hospital Los Angeles is a 501(c)(3) nonprofit hospital for pediatric...
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262 Danny Thomas Pl
Memphis, Tennessee 38105
(901) 495-3300
St. Jude Children's Research Hospital St. Jude is unlike any other pediatric treatment and research...
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Boston, Massachusetts 02115
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1801 Inwood Rd
Dallas, Texas 75390
(214) 645-3300
University of Texas Southwestern Medical Center UT Southwestern is an academic medical center, world-renowned for...
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1275 York Ave
New York, New York 10021
(212) 639-2000
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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Orlando, Florida 32827
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4800 Sand Point Way NE
Seattle, Washington 98105
(206) 987-2000
Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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Sydney, New South Wales
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