Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000060640
Ethics application status
Approved
Date submitted
13/01/2014
Date registered
20/01/2014
Date last updated
24/11/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
An open-label, multi-centre Phase I study of the safety and tolerability of intravenously (IV) infused PG545 in patients with advanced solid tumours
Scientific title
Study of the safety and tolerability of IV infused PG545 in patients with advanced solid tumours
Secondary ID [1] 283872 0
PG545102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumours 290856 0
Condition category
Condition code
Cancer 291217 291217 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Once weekly PG545 administered via a 1 hour IV infusion. Subjects will be treated until they exhibit disease progression or are discontinued for reasons of tolerability. Multiple ascending dose study with Cohort 1 receiving 25 mg/week; Cohort 2: 50 mg/week; Cohort 3: 100 mg/week; Cohort 4: 150 mg/week; Cohort 5: 200 mg/week; Cohort 6: 250 mg/week.
Intervention code [1] 288547 0
Treatment: Drugs
Comparator / control treatment
Uncontrolled
Control group
Uncontrolled

Outcomes
Primary outcome [1] 291211 0
Determination of Maximum tolerated dose (MTD) based on dose limiting toxicities (DLT)
Timepoint [1] 291211 0
Evaluated at the end of the first 1 month cycle
Secondary outcome [1] 306242 0
Assessment of safety and tolerability of PG545 when administered by once weekly IV infusion following multiple doses. Determined by frequency and severity of adverse events and collection of laboratory safety data.
Timepoint [1] 306242 0
Continuously throughout treatment and up until one month following final dose.
Secondary outcome [2] 306243 0
Estimate pharmacokinetic parameters of PG545 when administered by once weekly intravenous infusion (by plasma assay) and explore pharmacokinetic / pharmacodynamic relationships (plasma samples assaying target molecules, including but not limited to heparanase, VEGF, VEGFR, FGF2, and IL-12)
Timepoint [2] 306243 0
Assessed at 30 minutes, 2, 4, 6, 24, 48, 72, 144, and 168 hours post-infusion during weeks one and four of dosing, at the end of each cycle and at the end of study.
Secondary outcome [3] 306244 0
To document any anti-tumour activity observed as per RECIST criteria
Timepoint [3] 306244 0
Every eight weeks throughout treatment and up to four weeks post-treatment.

Eligibility
Key inclusion criteria
- Age 18 years and older.
- Histological or cytological documentation of non haematological, malignant solid tumour, excluding primary brain or spinal tumours.
- Subjects with advanced solid tumours who have failed all standard therapies, no longer are candidates for standard therapy, have no standard therapy available, or choose not to pursue standard therapy (the later is to be documented).
- Measurable disease (at least 1 target lesion) according to RECIST 1.1.
- Life expectancy of at least 12 weeks.
- ECOG Performance Status of 0 or 1.
- Written, signed and dated informed consent to participate in study.
- Able and willing to meet all protocol-required treatments, investigations and visits.
- Have adequate organ function including: Bone Marrow Reserve: Total white blood cell (WBC) count greater than or equal to 2300 cells/microL, absolute neutrophil count (ANC) greater than or equal to 1500 cells/microL, platelets greater than or equal to 100,000/microL, haemoglobin greater than or equal to 9 g/dL; Hepatic: Bilirubin less than or equal to 1.5 x upper limits of normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) less than or equal to 2.5 x ULN – if liver metastases are present then less than or equal to 5 x ULN; Renal: serum creatinine less than or equal to 1.5 times ULN - subjects with a serum creatinine greater than 1.5 x ULN may be enrolled if their creatinine clearance is calculated or measured at greater than 60 mL/minute; Coagulation: Activated partial thromboplastin time (APTT) and prothrombin time (PT) less than or equal to 1.2 x ULN.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Clinically significant non-malignant disease including, but not limited to, major surgery within 6 weeks of randomisation, active clinically significant infection, myocardial infarction within 6 months prior to randomisation, cerebrovascular event or transient ischaemic attack within 12 months prior to randomisation or clinically significant gastrointestinal bleeding within 12 months prior to randomisation. Anti-cancer therapy within 4 weeks of Cycle 1 day 1 (excluding GnRH agonists for prostate cancer). Palliative radiation for bone metastases within 2 weeks of Cycle 1 day 1.
- Active CNS metastases. Subjects with prior CNS metastases treated by surgery and/or stereotactic irradiation are eligible providing they have no evidence of active disease at screening. Subjects with prior CNS metastases treated with only whole brain radiation therapy are ineligible.
- Subjects with uncontrolled diabetes.
- History of allergy and / or hypersensitivity and / or other clinically significant adverse drug reaction to heparin or other anti-coagulant agents.
- History of immune-mediated thrombocytopaenia or other platelet abnormalities or other hereditary or acquired coagulopathies, or laboratory evidence of anti-heparin antibodies, or any previous history of having tested positive for anti-heparin antibodies.
- Concomitant use of aspirin (> 150 mg/day), non steroidal anti-inflammatory drugs (except COX-2 selective inhibitors), vitamin K antagonists (other than low-dose prophylactic use), heparin within two weeks prior to randomisation, or other anti-platelet drugs (e.g. abciximab, clopidogrel, dipyridamole, ticlopidine and tirofiban). Low-dose aspirin (= 150 mg/day) and low dose prophylactic vitamin K antagonists (e.g. warfarin = 1 mg/day) are permitted as concomitant medications.
- History of severe allergic, anaphylactic or other significant adverse reaction to radiographic contrast media (iodinated or non-iodinated), which cannot be managed by pre treatment with agents such as steroids or anti histamines, and which, in the opinion of the Investigator, renders the subject unsuitable for routine CT or MRI scanning. Subjects who are contra-indicated for CT or MRI scanning for other reasons (e.g. ferromagnetic implants, profound claustrophobia), should not be enrolled.
- Known seropositivity to the human immunodeficiency virus (HIV).
- Women who are pregnant or breast-feeding.
- Women of child-bearing potential and male subjects who are partners of women of childbearing potential who are unable or unwilling to practice a highly effective means of contraception. Effective birth control includes: a) birth control pills, depot progesterone, or an intrauterine device plus one barrier method, or b) two barrier methods. Effective barrier methods are: male and female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).
- Active substance abuse, including alcohol, which, in the opinion of the Investigator, risks impairing the ability of the subject to comply with the protocol.
- Subjects who have received an investigational agent within 28 days prior to Cycle 1 Day 1; or are currently participating in any other clinical study or research project which involves administration of a pharmaceutical product or experimental treatment, or which involves protocol-specified laboratory tests, imaging studies or other investigations.

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
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/12/2013
Actual
31/12/2013
Date of last participant enrolment
Anticipated
31/10/2014
Actual
2/05/2016
Date of last data collection
Anticipated
28/10/2016
Actual
22/09/2016
Sample size
Target
25
Accrual to date
Final
23
Recruitment in Australia
Recruitment state(s)
WA,VIC

Funding & Sponsors
Funding source category [1] 288515 0
Commercial sector/Industry
Name [1] 288515 0
Progen Pharmaceuticals Ltd
Country [1] 288515 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Progen Pharmaceuticals Ltd
Address
2806 Ipswich Road, Darra, QLD 4076
Country
Australia
Secondary sponsor category [1] 287221 0
None
Name [1] 287221 0
Address [1] 287221 0
Country [1] 287221 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290379 0
Bellberry Limited
Ethics committee address [1] 290379 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 290379 0
Australia
Date submitted for ethics approval [1] 290379 0
Approval date [1] 290379 0
25/10/2013
Ethics approval number [1] 290379 0

Summary
Brief summary
This study aims to establish the maximum tolerated dose of PG545 and to evaluate its safety in subjects with advanced solid tumours.

Who is it for? You may be eligible to join this study if you are a male or female aged 18 years or above who has been diagnosed with a non haematological malignant solid tumour, excluding primary brain or spinal tumours. To be eligible patients must have failed all standard therapies, no longer be a candidate for standard therapy, have no standard therapy available, or have chosen not to pursue standard therapy.

Study details: All participants in this study will receive the drug PG545 once weekly via a 1 hour intravenous infusion (i.e. directly into the vein). Subjects will be treated until either disease progresses or they can't have further treatment due to tolerability. They will be regularly monitored throughout the treatment period in order to determine the safety and tolerability of treatment. The dose of PG545 will also be increased in new groups of patients in order to determine the maximum tolerated dose. In addition the study will explore whether PG545 exposure results in changes to chemicals produced by the body that are associated with cancer growth and spread. This is the first clinical study of PG545 administered by intravenous infusion.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 45398 0
Prof Michael Millward
Address 45398 0
Sir Charles Gairdner Hospital, 1st Floor, B Block, Hospital Avenue, Nedlands WA 6009
Country 45398 0
Australia
Phone 45398 0
+ 61 (08) 6382 5100
Fax 45398 0
Email 45398 0
[email protected]
Contact person for public queries
Name 45399 0
Hamza Cakan
Address 45399 0
Linear Clinical Research Ltd, 1st Floor, B Block, Hospital Avenue, Nedlands WA 6009
Country 45399 0
Australia
Phone 45399 0
+ 61 (08) 6382 5100
Fax 45399 0
Email 45399 0
[email protected]
Contact person for scientific queries
Name 45400 0
Keith Dredge
Address 45400 0
Progen Pharmaceuticals Ltd, 2806 Ipswich Rd, DARRA, QLD, AUSTRALIA, 4076
Country 45400 0
Australia
Phone 45400 0
+61 (07) 3273 9179
Fax 45400 0
Email 45400 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.