Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12616000008426
Ethics application status
Approved
Date submitted
1/07/2015
Date registered
12/01/2016
Date last updated
12/01/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of RX108 in Patients with Advanced or Metastatic Solid Tumours.
Scientific title
A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of RX108 in Patients with Advanced or Metastatic Solid Tumours.
Secondary ID [1] 287031 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced or Metastatic Solid Tumours 295497 0
Condition category
Condition code
Cancer 295754 295754 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
RX108 will be administered as a two hour IV infusion, and the starting dose will be 0.02 mg/m2/day.
Increase of 0.02mg/m2/day per each cohort up to maximum tolerated dose. This is a single dose IV per participant.. One patient recruited per each cohort.
Intervention code [1] 292239 0
Treatment: Drugs
Comparator / control treatment
no treatment
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295468 0
To evaluate the safety and tolerability of single and multiple doses of RX108 administered by intravenous (IV) infusion to patients with locally advanced or metastatic solid tumours.
Outcomes will be assessed via: up yo three measurable and evaluable lesions should be assessed and documented, using physical examination and image based evaluation.
Screening assessments will include Computed Tomorgraphy (CT) scans with oral and IV contrast of the chest, abdomen, and pelvis, and a brain scan (CT or Magnetic Resonance Imaging (MRI)). Bone scans and CT scan of neck should also be performed if clinically indicated.. Disease status will be assessed using Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1. Other methods of assessment of measurable disease as per RECIST may be used.
Adverse events assessment: medical and scientific judgment will be exercised in deciding whether reporting is appropriate in other situations, such as important medical events that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require medical or surgical intervention.
Timepoint [1] 295468 0
Baseline and 30 days and 7 months after intervention commencement
Primary outcome [2] 296128 0
To determine the Maximum Tolerated Dose (MTD) of RX108 if possible; if an MTD is not reached, an optimum biological dose will be determined (after the safety review committee (SRC) and Investigators discuss the optimal balance between the dose (pharmacokinetic (PK) parameters), toxicity and biomarker studies confirming target effect). MTD will be determined by the SRC, reviewing the chart and AE log.
Timepoint [2] 296128 0
Baseline and 30 days and 7 months after intervention commencement
Secondary outcome [1] 315644 0
To characterize the PK of single doses of RX108 administered by IV infusion in patients with locally advanced or metastatic solid tumours. Outcome will be assessed via the PK blood sample collection.
Timepoint [1] 315644 0
Baseline and 30 days and 7 months after intervention commencement
Secondary outcome [2] 317563 0
To investigate potential biomarkers (e.g. PI3K, pAKT, ccfDNA and CTC) for the action of RX108 via serum assay.
Timepoint [2] 317563 0
Baseline and 30 days and 7 months after intervention commencement

Eligibility
Key inclusion criteria
1. Signed Informed Consent Form
2. Age > 18 years
3. Histologically or cytologically documented cancer
4. Incurable, locally advanced, or metastatic solid malignancy that has progressed on, or failed at least one prior systemic therapy or have refused systemic treatment
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Male or female patients of child-producing potential must agree to use double barrier contraception: condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD), contraceptives (oral, implants or injectable) or other avoidance of pregnancy measures during the study and for 90 days after the last day of treatment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any clinically significant cardiovascular disease including but not limited to:
*New York Heart Association Class II or greater congestive heart failure;
*History of ischaemic cardiac disease, myocardial infarction or unstable angina within 6 months prior to Day 1;
- Hypertrophic obstructive cardiomyopathy;
- History of stroke or transient ischemic attack within 6 months prior to Day 1;
*Presence or history of cardiac conduction abnormalities (increased PR or QRS), atrioventricular block or arrhythmias including intermittent complete heart block or second degree atrioventricular block, history of Stokes-Adams attacks, ventricular tachycardia, ventricular fibrillation or supraventricular arrhythmias;
2. Use of the following concurrent medications: beta blockers, digoxin, calcium channel blockers, amiodarone, flecainide, quinidine, and any other anti-arrhythmic.
3. Known contra-indication, intolerance or hypersensitivity to digoxin
4. Inadequate hematologic and organ function, defined by the following
*Absolute neutrophil count < 1.5x109/L, haemoglobin < 9 g/dL
*Total bilirubin 1.5 x the upper limit of normal (ULN) with the following exception: Patients with known Gilbert disease who have serum bilirubin level > 3 x the ULN and normal Aspartate Transaminase (AST)/ Alanine Transaminase (ALT) may be enrolled.
*AST and/or ALT > 2.5 x the ULN with the following exception: Patients with documented liver metastases may have AST and/or ALT levels > 5 x the ULN.
*Serum creatinine > 1.5 x the ULN with the following exception: A creatinine clearance of 50 mL/min based on a calculated glomerular filtration rate (GFR) (e.g. Cockcroft-Gault formula)
*International normalized ratio (INR) > 1.5 x the ULN or activated partial thromboplastin time (aPTT) > 1.5 x the ULN. The INR applies only to patients who do not receive therapeutic anti-coagulation.
*Serum electrolytes (Sodium, Calcium, Potassium, Magnesium) within normal limits.
5. Severe respiratory disease.
6. Any unapproved concurrent therapies for cancer (complementary or alternative therapies), or any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, radiotherapy, or herbal therapy within 4 weeks prior to initiation of study treatment with the following exceptions:
*Hormonal therapy with gonadotropin-releasing hormone agonists for prostate cancer at stable doses for at least 30 days prior to study entry
*Hormone-replacement therapy or oral contraceptives at stable doses for at least 30 days prior to study entry
*Palliative radiation to bone metastases acceptable within 2 weeks prior to Day 1
7. AEs from prior anti-cancer therapy that have not resolved to CTCAE Grade 1, except for alopecia.
8. Clinically significant active infection.
9. Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
10. Known human immunodeficiency virus infection.
11. Pregnant (positive pregnancy test) or lactating women.
12. Active or untreated brain metastasis.
13. Inability to comply with study and follow-up procedures.
14. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the Investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.

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
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/04/2015
Actual
3/06/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
35
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 291581 0
Commercial sector/Industry
Name [1] 291581 0
Suzhou NeuPharma Co., Ltd.
Country [1] 291581 0
China
Primary sponsor type
Commercial sector/Industry
Name
Suzhou NeuPharma Co., Ltd.
Address
Suite C15-501, 218 Xinghu Road,
Suzhou Industrial Park
Suzhou, China 215123
Country
China
Secondary sponsor category [1] 290253 0
Commercial sector/Industry
Name [1] 290253 0
INC Research Australia Pty Ltd
Address [1] 290253 0
159 Port Road
Hindmarsh SA 5007
Country [1] 290253 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294105 0
SWSLHD Human Research Ethics Committee
Ethics committee address [1] 294105 0
Ethics committee country [1] 294105 0
Australia
Date submitted for ethics approval [1] 294105 0
27/10/2014
Approval date [1] 294105 0
05/03/2015
Ethics approval number [1] 294105 0
HREC/14/LPOOL/492

Summary
Brief summary
This study will determine the safety and pharmacokinetics of the investigational drug RX108 in patients with advanced or metastatic solid tumours. Who is it for? You may be eligible to join this study if you are aged 18 years or above and have been diagnosed with an incurable, locally advanced or metastatic solid tumour that has progressed or failed at least one prior systemic therapy or have refused systemic treatment. Study details All participants will receive the investigational drug RX108 through intravenous infusion at a low dose and will be escalated. Each participant will only receive a single dose, depending on the cohort into which they are recruited. The study will use an accelerated dose escalation design using single patient cohorts until a single related toxicity of Grade = 3 or a Dose Limiting Toxicity (DLT) is observed. Safety and tolerability of RX108 will be assessed by such as physical examination, vital signs, ECG, and clinical
laboratory testing at 30 days and 7 months post intervention commencement. Maximum tolerated dose will be determined via the safety review committee (SRC) and Investigators review the optimal balance between the dose (pharmacokinetic (PK) parameters), toxicity and biomarker studies confirming target effect. Participants will be followed-up until 7 months post intervention commencement to investigate potential biomarkers for RX108.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58542 0
Prof Paul De Souza
Address 58542 0
Cancer Therapy Centre
Liverpool Hospital
Elizabeth Street
Liverpool NSW 2170
Country 58542 0
Australia
Phone 58542 0
+61 (0)2 8738 9744
Fax 58542 0
Email 58542 0
[email protected]
Contact person for public queries
Name 58543 0
Ms Sooma Jafari
Address 58543 0
INC Research
Level 1, 20 Atherton Road
Oakleigh VIC 3166
Country 58543 0
Australia
Phone 58543 0
+61 (0)3 8533 6804
Fax 58543 0
Email 58543 0
[email protected]
Contact person for scientific queries
Name 58544 0
Ms Sooma Jafari
Address 58544 0
INC Research
Level 1, 20 Atherton Road
Oakleigh VIC 3166
Country 58544 0
Australia
Phone 58544 0
+61 (0)3 8533 6804
Fax 58544 0
Email 58544 0
[email protected]

No information has been provided regarding IPD availability


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.