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

Phase 1
Conditions
Locally Advanced Solid Tumors
Metastatic Solid Tumors
Interventions
Registration Number
NCT03646071
Lead Sponsor
NeuPharma, Inc.
Brief Summary

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

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
80
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose Escalation PhaseRX108The Dose-Escalation Phase will employ a standard 3+3 algorithm to investigate ascending dose cohorts of RX108.
Dose Expansion PhaseRX108In the Expansion Phase, subjects will receive RX108 at the maximum tolerated dose.
Primary Outcome Measures
NameTimeMethod
Part 2: Incidence of adverse events (AEs) and serious adverse events (SAEs).Day 1 to 30 days post last dose

The incidence of adverse events (AEs) and serious adverse events (SAEs) for each cohort dose will be assessed using CTCAE v 5.0.

Part 1: Maximum tolerated dose (MTD) of RX108Day 1 to 30

All patients treated with RX108 across all dosing levels will have safety assessed in order to determine the MTD.

Secondary Outcome Measures
NameTimeMethod
Elimination half-life (T1/2)Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8

Pharmacokinetics parameter

Systemic clearance (CL)Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8

Pharmacokinetics parameter

Area under the plasma concentration-time curve (AUC)Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8

Pharmacokinetics parameter

Maximum observed plasma concentration (Cmax) of RX108Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8

Pharmacokinetics parameter

Time to reach maximum concentration (Tmax)Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8

Pharmacokinetics parameter

Response rate (per RECIST v1.1)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.

Evaluate the preliminary efficacy of RX108 in subjects with locally advanced or metastatic solid tumors (subjects with measurable disease in Part 2).

Trial Locations

Locations (2)

Cedars-Sinai

🇺🇸

Los Angeles, California, United States

University of Texas at MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

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