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

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT02122913

Collaborator

(none)

Enrollment

Locations

Arms

83.2

Actual Duration (Months)

9.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors Harboring NTRK Fusion	Drug: Larotrectinib (Vitrakvi, BAY2757556)	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of the Oral TRK Inhibitor Larotrectinib in Adult Patients With Solid Tumors

Actual Study Start Date :

May 4, 2014

Actual Primary Completion Date :

Feb 1, 2017

Actual Study Completion Date :

Apr 9, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tumor patients_Dose 1 Adult patients with solid tumors receiving 50 mg of BAY2757556 once daily (dose escalation cohort).	Drug: Larotrectinib (Vitrakvi, BAY2757556) BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles. Other Names: LOXO-101
Experimental: Tumor patients_Dose 2 Adult patients with solid tumors receiving 100 mg of BAY2757556 once daily (dose escalation cohort).	Drug: Larotrectinib (Vitrakvi, BAY2757556) BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles. Other Names: LOXO-101
Experimental: Tumor patients_Dose 3 Adult patients with solid tumors receiving 100 mg of BAY2757556 twice daily (dose escalation cohort).	Drug: Larotrectinib (Vitrakvi, BAY2757556) BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles. Other Names: LOXO-101
Experimental: Tumor patients_Dose 4 Adult patients with solid tumors receiving 200 mg of BAY2757556 once daily (dose escalation cohort).	Drug: Larotrectinib (Vitrakvi, BAY2757556) BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles. Other Names: LOXO-101
Experimental: Tumor patients_Dose 5 Adult patients with solid tumors receiving 150 mg of BAY2757556 twice daily (dose escalation cohort).	Drug: Larotrectinib (Vitrakvi, BAY2757556) BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles. Other Names: LOXO-101
Experimental: Tumor patients_Dose 6 Adult patients with solid tumors receiving 200 mg of BAY2757556 twice daily (dose escalation cohort).	Drug: Larotrectinib (Vitrakvi, BAY2757556) BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles. Other Names: LOXO-101
Experimental: Tumor patients_Expansion 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.	Drug: Larotrectinib (Vitrakvi, BAY2757556) BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles. Other Names: LOXO-101

Outcome Measures

Primary Outcome Measures

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

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
Duration of Response (DOR) [Up to 60 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado	Aurora	Colorado	United States	80045
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
4	Oregon Health and Science University	Portland	Oregon	United States	97239
5	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
6	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15232
7	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
8	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030