A study to test the safety and efficacy of the drug larotrectinib for the treatment of tumors with NTRK-fusion in children.

Phase 1

• Conditions: Solid tumors harboring NTRK fusion; MedDRA version: 21.0Level: LLTClassification code 10007959Term: Central nervous system neoplasm NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10007958Term: Central nervous system neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.1Level: HLTClassification code 10007960Term: Central nervous system neoplasms malignant NECSystem Organ Class: 100000004852; MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: PTClassification code 10081769Term: NTRK gene fusion overexpressionSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-003498-16-NL
• Lead Sponsor: Bayer Consumer Care AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-01-23
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 174

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
Are the trial subjects under 18? yes
Number of subjects for this age range: 161
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 13
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

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 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 CYP3A4 inhibitor or inducer other than those allowed per Section 6.3.2 of the study protocol.
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 TRK inhibitor for less than 28 days of treatment and discontinued because of intolerance remain eligible.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified