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 10007959Term: Central nervous system neoplasm NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); 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: 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-GB
• Lead Sponsor: Bayer Consumer Care AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-01-04
• Last Update Posted: 18 August 2020

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 174

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 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
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.
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 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 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.
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 performed within 28 days before C1D1 while on stable dose steroid medication for at least 7 days immediately before and during 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 CSF or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG).
4. Evaluable and/or measurable disease
a) Phase 1: Patients must have evaluable and/or measurable disease as defined by RECIST, RANO, or INRC.
b) Phase 2: Patients with a solid or CNS tumor or neuroblastoma must have at least one measurable lesion as defined by RECIST 1.1, RANO, or INRC.
5. Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50.
6. Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
7. An archival tumor tissue sample

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 and able to tolerate oral medications.
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