A Study of TRK-950 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLTs) of TRK-950 as single agent To establish the dose of TRK-950 recommended for future phase 2 studies

Detailed Description
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This study is a first-in-human study of TRK-950 in patients with advanced solid tumors and is primarily designed to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of TRK-950 administered via intravenous (IV) infusion once weekly for 3 weeks every 28 days in Arm 1. Once enrollment in Arm 1 was completed, two dose schedules will be evaluated in Arm 2 to determine the dosing schedule. Up to six (6) patients will be enrolled respectively. In parallel, to determine anti-tumor activity up to twelve (12) patients will be enrolled in Arm 3.

Official Title
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A Phase 1, Multicenter, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of TRK-950 Given Intravenously in Patients With Advanced Solid Tumors

Conditions
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Locally Advanced or Metastatic Solid Carcinomas, Colon Cancer, Cholangiocarcinoma

Intervention / Treatment
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* Biological: TRK-950
* Biological: TRK-950
* Biological: TRK-950


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed locally advanced or metastatic solid carcinomas in Arm 1 Patients with histologically confirmed locally advanced or metastatic colon cancer in Arm 2 Patients with histologically confirmed locally advanced or metastatic cholangiocarcinomas in Arm 3 Tumor progression after receiving standard/approved chemotherapy or where there is no approved therapy or not amendable to a curative treatment Measurable disease per RECIST 1.1 (primary or metastases) Exclusion Criteria: New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy Pregnant or nursing women Treatment with radiation therapy, surgery, chemotherapy, immunotherapy, or investigational therapy within four weeks prior to study entry Unwillingness or inability to comply with procedures required in this protocol Known active infection with HIV, hepatitis B, hepatitis C Symptomatic brain metastases Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the sponsor Patients who are currently receiving any other investigational agent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 - TRK-950<br>Solid tumor TRK-950 (Three dose levels will be explored during Arm 1) | Biological: TRK-950<br>* Intravenously over 60 minutes, on day 1, 8 and 15 of each cycle<br>|
| Experimental: Arm 2 - TRK-950<br>Colon cancer TRK-950 (Low dose and High dose) | Biological: TRK-950<br>* Low dose: intravenously over 60 minutes, on day 1, 8, 15 and 22 of each cycle High dose: intravenously over 60 minutes, on day 1 and 15 of each cycle<br>|
| Experimental: Arm 3 -TRK-950<br>Cholangiocarcinomas TRK-950 (Low dose) | Biological: TRK-950<br>* Low dose: Intravenously over 60 minutes, on day 1, 8, 15 and 22 of each cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event |  | through study completion, an average of 1 year | 
| CTCAE version 4.03 |  | through study completion, an average of 1 year | 
| Blood pressure (mmHg) |  | through study completion, an average of 1 year | 
| Heart rate (bpm) |  | through study completion, an average of 1 year | 
| Respiratory rate (bpm) |  | through study completion, an average of 1 year | 
| Temperature (°F or °C) |  | through study completion, an average of 1 year | 
| Weight (lbs/kg) |  | through study completion, an average of 1 year | 
| Height (inches/cm) |  | through study completion, an average of 1 year | 
| Karnofsky performance status |  | through study completion, an average of 1 year | 
| Electrocardiogram |  | through study completion, an average of 1 year | 
| Clinical laboratory tests |  | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration curve(AUC) |  | through study completion, an average of 1 year | 
| Maximum plasma concentration(Cmax) |  | through study completion, an average of 1 year | 
| Time to maximum plasma concentration(Tmax) |  | through study completion, an average of 1 year | 
| Terminal elimination half life(t1/2) |  | through study completion, an average of 1 year | 
| Total body clearance(CL) |  | through study completion, an average of 1 year | 
| Apparent volume of distribution(Vd) |  | through study completion, an average of 1 year | 
| Tumor response rate |  | through study completion, an average of 1 year | 
| Duration of response |  | through study completion, an average of 1 year | 
| Time to progression |  | through study completion, an average of 1 year | 
| Progression free survival |  | through study completion, an average of 1 year |