A Study to Test the Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer

Phase 1

Completed

• Conditions: Solid Tumors Harboring NTRK Fusion
• Interventions: Drug: Larotrectinib (Vitrakvi, BAY2757556)

• Registration Number: NCT02122913
• Lead Sponsor: Bayer

Brief Summary

This research study is done to test the safety of the drug larotrectinib in adult cancer patients. The drug may be used to treat cancer with a change in a particular gene (NTRK1, NTRK2 or NTRK3), because it blocks the action of these genes in cancer cells. The study also investigates how the drug is absorbed and processed in the human body. This is the first study to test larotrectinib in humans with cancer, for whom no other effective therapy exists.

Detailed Description

The trial will be conducted in 2 parts: an initial dose escalation phase of larotrectinib in subjects with advanced solid tumors will be followed by an expansion phase in subjects with solid tumors having a NTRK fusion.

The objectives of the study are to determine the safety, pharmacokinetic profile, recommended dose and efficacy of orally administered larotrectinib in patients with NTRK fusions.

Study Timeline

• Study First Submitted: 2014-04-16
• Study First Submitted QC: 2014-04-24
• Study First Posted: 2014-04-25
• Study Start: 2014-05-04
• Primary Completion: 2017-02-01
• Study Completion: 2021-04-09
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-02
• Last Update Posted: 2023-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

• Adult patients with a locally advanced or metastatic solid tumor that has progressed or was nonresponsive to available therapies, are unfit for standard chemotherapy or for which no standard or available curative therapy exists
• Proof of a malignancy harboring a NTRK fusion
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 and a life expectancy of at least 3 months
• Adequate hematologic, hepatic, and renal function

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Exclusion Criteria

• Patients with unstable primary central-nervous-system tumors or metastasis, exceptions possible
• Clinically significant active cardiovascular disease or history of myocardial infarction
• Active uncontrolled systemic bacterial, viral, or fungal infection
• Current treatment with a strong CYP3A4 inhibitor or inducer
• Pregnancy or lactation

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Tumor patients_Dose 3	Larotrectinib (Vitrakvi, BAY2757556)	Adult patients with solid tumors receiving 100 mg of BAY2757556 twice daily (dose escalation cohort).
Tumor patients_Dose 1	Larotrectinib (Vitrakvi, BAY2757556)	Adult patients with solid tumors receiving 50 mg of BAY2757556 once daily (dose escalation cohort).
Tumor patients_Dose 2	Larotrectinib (Vitrakvi, BAY2757556)	Adult patients with solid tumors receiving 100 mg of BAY2757556 once daily (dose escalation cohort).
Tumor patients_Dose 4	Larotrectinib (Vitrakvi, BAY2757556)	Adult patients with solid tumors receiving 200 mg of BAY2757556 once daily (dose escalation cohort).
Tumor patients_Dose 5	Larotrectinib (Vitrakvi, BAY2757556)	Adult patients with solid tumors receiving 150 mg of BAY2757556 twice daily (dose escalation cohort).
Tumor patients_Dose 6	Larotrectinib (Vitrakvi, BAY2757556)	Adult patients with solid tumors receiving 200 mg of BAY2757556 twice daily (dose escalation cohort).
Tumor patients_Expansion	Larotrectinib (Vitrakvi, BAY2757556)	Adults patients with solid tumors and neurotrophic tyrosine kinase (NTRK) genes or proteins of types 1 - 3 (dose expansion cohort). Patients receive either the recommended or maximum tolerated dose of BAY2757556 as determined in the dose escalation part.

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events	25 months
Severity of adverse events	25 months	The severity of adverse events will be assesssed according to the NCI CTCAE version 4.03.
Maximum tolerated dose (MTD)	25 months
Recommended dose for dose expansion	25 months

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR)	Up to 60 months
Maximum concentration of larotrectinib in plasma (Cmax)	Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
Time to maximum concentration of larotrectinib in plasma (Tmax)	Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
Half-life of larotrectinib in plasma (t1/2)	Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
Area under the concentration versus time curve of larotrectinib in plasma (AUC)	Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
Overall Response Rate (ORR)	Up to 60 months	Assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-Oncology (RANO) as appropriate

Trial Locations

Locations (8)

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States