A Phase 1/2 Clinical Trial of Pediatric Cancer Patients With Solid Tumors Treated with Larotrectinib

Phase 1

• Conditions: Central Nervous System Neoplasms and advanced solid tumors; MedDRA version: 21.0Level: LLTClassification code 10049516Term: Malignant tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); 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; Therapeutic area: Diseases [C] - Cancer [C04]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-03-08
• Last Update Posted: 21 June 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 174

Inclusion Criteria

Starting from Protocol Version 11 (10 JUL 2019), newly enrolled patients will only enter Phase 2.
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 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 for which no standard or systemic curative therapy exists or
Phase 2: Patients with locally advanced or metastatic 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 for whIch no standard or available systemic curative therapy exists, with a documented NTRK gene fusion e.g. by NGS or in case of IFS, CMN or SBC with documented ETV6 rearrangement (or NTRK3 rearangement after discussion with the sponsor) by FISH or RT-PCR. Documented NTRK fusion by NGS shall 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.
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
Willingness of male and female patients with reproductive potential to utilize double effective birth control methods for the duration of treatment and for 1 month following study completion
Ability to swallow capsules, liquid or gastric access via a naso- or gastric tube
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