Description:
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.
Title
- Brief Title: A Study to Test the Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer
- Official Title: A Phase 1 Study of the Oral TRK Inhibitor Larotrectinib in Adult Patients With Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
20288
- SECONDARY ID:
LOXO-TRK-14001
- NCT ID:
NCT02122913
Conditions
- Solid Tumors Harboring NTRK Fusion
Interventions
| Drug | Synonyms | Arms |
|---|
| Larotrectinib (Vitrakvi, BAY2757556) | LOXO-101 | Tumor patients_Dose 1 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Tumor patients_Dose 1 | Experimental | Adult patients with solid tumors receiving 50 mg of BAY2757556 once daily (dose escalation cohort). | - Larotrectinib (Vitrakvi, BAY2757556)
|
| Tumor patients_Dose 2 | Experimental | Adult patients with solid tumors receiving 100 mg of BAY2757556 once daily (dose escalation cohort). | - Larotrectinib (Vitrakvi, BAY2757556)
|
| Tumor patients_Dose 3 | Experimental | Adult patients with solid tumors receiving 100 mg of BAY2757556 twice daily (dose escalation cohort). | - Larotrectinib (Vitrakvi, BAY2757556)
|
| Tumor patients_Dose 4 | Experimental | Adult patients with solid tumors receiving 200 mg of BAY2757556 once daily (dose escalation cohort). | - Larotrectinib (Vitrakvi, BAY2757556)
|
| Tumor patients_Dose 5 | Experimental | Adult patients with solid tumors receiving 150 mg of BAY2757556 twice daily (dose escalation cohort). | - Larotrectinib (Vitrakvi, BAY2757556)
|
| Tumor patients_Dose 6 | Experimental | Adult patients with solid tumors receiving 200 mg of BAY2757556 twice daily (dose escalation cohort). | - Larotrectinib (Vitrakvi, BAY2757556)
|
| Tumor patients_Expansion | Experimental | 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. | - Larotrectinib (Vitrakvi, BAY2757556)
|
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of participants with adverse events |
| Time Frame: | 25 months |
| Safety Issue: | |
| Description: | The severity of adverse events will be assesssed according to the NCI CTCAE version 4.03. |
Secondary Outcome Measures
| Measure: | Maximum concentration of larotrectinib in plasma (Cmax) |
| Time Frame: | Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1 |
| Safety Issue: | |
| Description: | |
| Measure: | Time to maximum concentration of larotrectinib in plasma (Tmax) |
| Time Frame: | Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1 |
| Safety Issue: | |
| Description: | |
| Measure: | Half-life of larotrectinib in plasma (t1/2) |
| Time Frame: | Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1 |
| Safety Issue: | |
| Description: | |
| Measure: | Area under the concentration versus time curve of larotrectinib in plasma (AUC) |
| Time Frame: | Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1 |
| Safety Issue: | |
| Description: | |
| Measure: | Overall Response Rate (ORR) |
| Time Frame: | Up to 60 months |
| Safety Issue: | |
| Description: | Assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-Oncology (RANO) as appropriate |
| Measure: | Duration of Response (DOR) |
| Time Frame: | Up to 60 months |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Bayer |
Trial Keywords
- Advanced solid tumors
- Neurotrophic tyrosine receptor kinase (NTRK)
- NTRK1
- NTRK2
- NTRK3
- Fusion Positive
- TRK fusion
- TRKA
- TRKB
- TRKC
- ETV6
Last Updated
May 12, 2021
