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Trial registered on ANZCTR


Registration number
ACTRN12623000307606
Ethics application status
Approved
Date submitted
2/02/2023
Date registered
21/03/2023
Date last updated
31/08/2023
Date data sharing statement initially provided
21/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I study to evaluate Safety and Tolerability of RX108-A Tablets in Patients with advanced Cancer
Scientific title
A Phase I, Open-Label Study of the Safety, Tolerability and Pharmacokinetics of RX108-A Tablet in Patients with Locally Advanced or Metastatic Solid Tumors
Secondary ID [1] 308593 0
NP-105
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced or Metastatic Solid Tumors 328462 0
Condition category
Condition code
Cancer 325495 325495 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
RX108- A novel synthetic small-molecule inhibitor of Na+/K+ -ATPase.
There are 2 parts to this study: Part 1, dose escalation; Part 2, dose expansion.
Part 1 – Dose Escalation: The starting dose will be 0.5 mg of RX108-A Tablet once daily and subsequent dose escalation will proceed with dose increases of 25% to 100% between cohorts up to maximum dose of 5 mg/day (tentatively), based on the safety data. Dosing will be continued until the Maximum Tolerated Dose (MTD) or optimum biological dose (OBD) is reached to provide a Recommended Phase 2 Dose (RP2D). A tablet/tablets administered orally once daily for 3 weeks, followed by 1 week of rest. Drug tablet return and accountability will monitor adherence
Part 2 – Dose Expansion: The expansion part will consist of patients with all solid tumors and up to an additional 6 to 9 patients treated at the RP2D. Part 2 will commence after RP2D (recommended phase 2 dose) is determined by the Safety Review Committee. As seen in Part 1, Part 2 will have a tablet/tablets administered orally once daily for 3 weeks, followed by 1 week of rest. Drug tablet return and accountability will be monitor adherence.

The time from Screening to last visit for each patient will be approximately 7 months. Treatment cycles of 28 days then proceed to the next dose up, for up to 7 months.
Intervention code [1] 325046 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333354 0
To evaluate the safety and tolerability of RX108-A Tablet administered orally once daily for 3 weeks followed by 1 week rest to patients with locally advanced or metastatic solid tumors via Dose-limiting toxicities. Safety and tolerability is assessed through ongoing physical exams, clinical laboratory tests (blood and urine samples), ECG, and evaluation of ECOG performance status during study visits.
Timepoint [1] 333354 0
Days 1, 8, 15 and 21 after being enrolled in the study and taking RX108-A
Primary outcome [2] 333355 0
To determine the Maximum Tolerated Dose (MTD) of RX108-A Tablet. The MTD is defined as the dose below the level at which > 33% of patients experience a dose-limiting toxicity (DLT) in a given cohort, and there will be at least six patients enrolled at the MTD to define safety. Toxicities will be assessed by physical exams, clinical laboratory tests (blood and urine samples), ECG, evaluation of ECOG performance status, and other tests if necessary.

Timepoint [2] 333355 0
Baseline, 30 days and 7 months after intervention commencement
Secondary outcome [1] 416739 0
To characterize the PK of oral RX108-A Tablet administered as multiple doses in patients with locally advanced or metastatic solid tumors via plasma samples via PK parameters: Cmax, Tmax, AUC0-last, AUC0-inf, T1/2, CL and Vss

Timepoint [1] 416739 0
Day 1 and Day 21 of Cycle 1: Pre-dose and 1, 2, 4, 6, 8 and 24 hours post dosing


Secondary outcome [2] 416745 0
To evaluate the preliminary efficacy of RX108-A Tablet via objective response rate as measured by the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria
Timepoint [2] 416745 0
Objective response rate – Defined as the rate of complete responses [CR] or partial responses [PR] per RECIST Version 1.1 as assessed by investigator from baseline (first dose) until disease progression or withdrawal from study
Secondary outcome [3] 418931 0
To evaluate the preliminary efficacy of RX108-A Tablet via duration of response. Disease control rate will be assesses by RECIST 1.1, duration of response
Timepoint [3] 418931 0
Duration of response – assessed per RECIST 1.1 by investigator from baseline (first dose) until disease progression or withdrawal from
Secondary outcome [4] 419415 0
To characterize the PK of oral RX108-A Tablet administered as multiple doses in patients with locally advanced or metastatic solid tumors via plasma samples via PK parameters: Cmax, Tmax, AUC0-last, AUC0-inf
Timepoint [4] 419415 0
Day 1 and Day 21 of Cycles 1, 2 and 3 only: Pre-dose and 1-2, 3-5 and 6-8 hours post dosing

Eligibility
Key inclusion criteria
A patient will be eligible for study participation if the patient meets all of the following criteria:
1. Signed Informed Consent Form.
2. 18 years and over.
3. Patients with locally advanced or metastatic solid tumors that have failed at least one standard of care therapy or were intolerant to, or have refused such treatment, are eligible.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Life expectancy of at least 3 months.
6. Must agree to use adequate contraception (females and males).

Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of certain cardiac abnormalities
2. History of inadequate pulmonary function
3. Symptomatic brain metastasis
4. Treatment with prohibited medications
5. Known contra-indication to digoxin
6. Treatment with any unapproved therapies for cancer, or any other anti-cancer therapy within 3 weeks
7. Any toxicity related to prior treatment must have resolved to Grade 1 or less, except for alopecia
8. Clinically significant active infection requiring systemic antibiotic treatment
9. Females who are pregnant or breastfeeding.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 25475 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [2] 25476 0
Nepean Hospital - Kingswood
Recruitment postcode(s) [1] 41288 0
2747 - Kingswood
Recruitment postcode(s) [2] 41287 0
3144 - Malvern

Funding & Sponsors
Funding source category [1] 312840 0
Commercial sector/Industry
Name [1] 312840 0
NeuPharma Pty Ltd
Country [1] 312840 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
NeuPharma Pty Ltd
Address
58 Gipps Street, Collingwood VIC 3066, Australia
Country
Australia
Secondary sponsor category [1] 314484 0
None
Name [1] 314484 0
Address [1] 314484 0
Country [1] 314484 0
Other collaborator category [1] 282501 0
Commercial sector/Industry
Name [1] 282501 0
Novotech (Australia) Pty Limited
Address [1] 282501 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 282501 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312118 0
Bellberry Limited HREC
Ethics committee address [1] 312118 0
123 Glen Osmond Road, Eastwood SA 5063, Australia
Ethics committee country [1] 312118 0
Australia
Date submitted for ethics approval [1] 312118 0
20/10/2022
Approval date [1] 312118 0
25/01/2023
Ethics approval number [1] 312118 0

Summary
Brief summary
This study is investigating a new cancer treatment drug, RX108-A, to determine whether it is safe and effective for patients with locally advanced or metastatic solid tumors.
Who is it for?: You may be eligible for this study if you are an adult aged 18 years or older and you have been diagnosed with locally advanced or metastatic solid tumors and you have failed at least one standard of care therapy, or you were intolerant to a standard of care therapy, or you have refused such treatment.

Study details: This study will firstly enroll participants into a dose escalation study. Participants who choose to enroll in the escalation study will be assigned a specific number of tablets to take each day for 3 weeks, followed by a 1 week rest. Participants will be asked to keep a diary of any side effects that they experience while taking the experimental treatment, and may be asked to stop taking the tablets if they experience any severe side effects. Participants will also be asked to provide blood samples at 4 different times during their 3-week treatment cycle. New groups of participants will be enrolled to test each higher dose of the experimental treatment until the best tolerated dose is identified.
After the best tolerated dose has been identified, a new group of up to 9 participants will be enrolled for the dose expansion study. Participants who choose to enroll in the expansion study will be assigned a specific number of tablets to take each day for 3 weeks, followed by a 1 week rest. Participants in this study will be asked to keep taking the tablets for 3-week cycles for up to 7 months, and will be asked to provide blood samples at different timepoints during their first three 3-week treatment cycles.

It is hoped this research will determine the highest safe dose of RX108-A that reduces the growth of tumors in people with locally advanced or metastatic solid tumors. If this study finds that RX108-A is safe and effective, it may be expanded to a larger trial of people with locally advanced or metastatic solid tumors.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123542 0
Prof Paul De Souza
Address 123542 0
Southside Cancer Care
3/533 Kingsway, Miranda NSW 2228, Australia
Country 123542 0
Australia
Phone 123542 0
+61 2 8556 9377
Fax 123542 0
Email 123542 0
P.DeSouza@westernsydney.edu.au
Contact person for public queries
Name 123543 0
Prof Paul De Souza
Address 123543 0
Southside Cancer Care
3/533 Kingsway, Miranda NSW 2228, Australia
Country 123543 0
Australia
Phone 123543 0
+61 2 8556 9377
Fax 123543 0
Email 123543 0
info@cancercarefoundation.org.au
Contact person for scientific queries
Name 123544 0
Prof Paul De Souza
Address 123544 0
Southside Cancer Care
3/533 Kingsway, Miranda NSW 2228, Australia
Country 123544 0
Australia
Phone 123544 0
+61 2 8556 9377
Fax 123544 0
Email 123544 0
info@cancercarefoundation.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.