A Study of RX108 in Patients With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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RX108 is a novel, potent, small-molecule inhibitor of Na+/K+-ATPase. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of RX108 in patients with locally advanced or metastatic solid tumors.

Detailed Description
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This is a open-label, two-part study comprised of a dose escalation part and a dose expansion part. In the dose escalation part, RX108 will be administered in ascending doses to evaluate the safety and tolerability of RX108 and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). The dose expansion part will assess the safety, pharmacokinetics, and efficacy of RX108 at the RP2D.

Official Title
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A Phase 1, Open-label Study of the Safety, Pharmacokinetics and Efficacy of RX108 in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions
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Locally Advanced Solid Tumors, Metastatic Solid Tumors

Intervention / Treatment
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* Drug: RX108


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed locally advanced or metastatic cancer that has failed all systemic therapies known to confer clinical benefit Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Minimum age of 18 years Adequate hematologic, hepatic and renal function Written Informed Consent Must agree to use adequate contraception (females and males) Exclusion Criteria: History of certain cardiac abnormalities History of inadequate pulmonary function Symptomatic brain metastasis Treatment with prohibited medications Known contra-indication to digoxin Treatment with any unapproved therapies for cancer, or any other anti-cancer therapy within 3 weeks Any toxicity related to prior treatment must have resolved to Grade 1 or less, with the exception of alopecia Clinically significant active infection requiring systemic antibiotic treatment Females who are pregnant or breastfeeding

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: Dose Escalation Phase<br>The Dose-Escalation Phase will employ a standard 3+3 algorithm to investigate ascending dose cohorts of RX108. | Drug: RX108<br>* RX108<br>|
| Experimental: Dose Expansion Phase<br>In the Expansion Phase, subjects will receive RX108 at the maximum tolerated dose. | Drug: RX108<br>* RX108<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Maximum tolerated dose (MTD) of RX108 | All patients treated with RX108 across all dosing levels will have safety assessed in order to determine the MTD. | Day 1 to 30 | 
| Part 2: Incidence of adverse events (AEs) and serious adverse events (SAEs). | The incidence of adverse events (AEs) and serious adverse events (SAEs) for each cohort dose will be assessed using CTCAE v 5.0. | Day 1 to 30 days post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) of RX108 | Pharmacokinetics parameter | Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8 | 
| Time to reach maximum concentration (Tmax) | Pharmacokinetics parameter | Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8 | 
| Area under the plasma concentration-time curve (AUC) | Pharmacokinetics parameter | Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8 | 
| Elimination half-life (T1/2) | Pharmacokinetics parameter | Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8 | 
| Systemic clearance (CL) | Pharmacokinetics parameter | Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8 | 
| Response rate (per RECIST v1.1) | Evaluate the preliminary efficacy of RX108 in subjects with locally advanced or metastatic solid tumors (subjects with measurable disease in Part 2). | Screening and every 2 cycles for the first 6 cycles and every 3 cycles thereafter (each cycle is 28 days), assessed up to 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally Advanced, Metastatic, Solid Tumor