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

Phase 1

• Conditions: Solid tumors harboring NTRK fusion; MedDRA version: 21.0Level: LLTClassification code: 10007959Term: Central nervous system neoplasm NOS Class: 10029104; MedDRA version: 21.1Level: LLTClassification code: 10065147Term: Malignant solid tumor Class: 10029104; MedDRA version: 20.1Level: HLTClassification code: 10007960Term: Central nervous system neoplasms malignant NEC Class: 10029205; MedDRA version: 21.0Level: PTClassification code: 10007958Term: Central nervous system neoplasm Class: 100000004864; MedDRA version: 23.0Level: PTClassification code: 10081769Term: NTRK gene fusion overexpression Class: 100000004850; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2022-502668-20-00
• Lead Sponsor: Bayer Consumer Care AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-10-13
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 155

Inclusion Criteria

Phase 1 (Closed): Phase 1: Birth through 21 years of age at cycle 1 day 1 (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 neurotrophic tyrosine kinase receptor (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 (IFS) who would require, in the opinion of the Investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection. 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 into this cohort must have a malignancy with a documented NTRK gene fusion with the exception of patients with IFS, congenital mesoblastic nephroma tumors (CMN) or secretory breast cancer (SBC). Patients with IFS, CMN or SBC may enroll into this cohort with documentation of an ETS variant gene 6 (ETV6) rearrangement by fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR) or a documented NTRK fusion by next generation sequencing (NGS)., Phase 2: Infants from birth and older at C1D1 with a locally advanced or metastatic IFS, patients with locally advanced IFS who would require, in the opinion of the Investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection withdocumented 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 exists, with a documented NTRK gene fusion e.g., by NGS, or in the case of IFS, CMN or SBC with documented ETV6 rearrangement (or NTRK3 rearrangement after discussion with the Sponsor) by FISH or RT-PCR. Documented NTRK fusion by NGS 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., 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., Malabsorption syndrome or other condition affecting oral absorption., 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., Pregnancy or lactation., Phase 2 Only: Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK, including entrectinib, repotrectinib, 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