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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Solid Tumors; Metastatic Solid Tumors
• Intervention / Treatment: Drug: RX108

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lyon Gleich, MD; Phone Number: 12400 (513) 579-9911; Email: l.gleich@medpace.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai
      • Contact: Vanessa Cajahuaringa; Phone Number: 310-967-2795; Email: vanessa.cajahuaringa@cshs.org
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas at MD Anderson Cancer Center
      • Contact: Lidong Liu, PhD; Email: lliu8@mdanderson.org
      • Principal Investigator: Siqing Fu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Phase; The Dose-Escalation Phase will employ a standard 3+3 algorithm to investigate ascending dose cohorts of RX108.	Drug: RX108; RX108
Experimental: Dose Expansion Phase; In the Expansion Phase, subjects will receive RX108 at the maximum tolerated dose.	Drug: RX108; RX108

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: NeuPharma, Inc.
• Investigators: Study Director: Lyon Gleich, MD, Medpace, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: July 18, 2018
• First Submitted That Met QC Criteria: August 22, 2018
• First Posted (Actual): August 24, 2018

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 12, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Metastatic; Locally Advanced; Solid Tumor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NP-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: To be determined.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No