Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000016932
Ethics application status
Approved
Date submitted
13/12/2010
Date registered
6/01/2011
Date last updated
8/12/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
An open-label, single-centre Phase I study of the safety and tolerability of PG545 in patients with advanced solid tumours
Scientific title
An open-label, single-centre Phase I study of the safety and tolerability of PG545 in patients with advanced solid tumours
Secondary ID [1] 253284 0
NCT01252095
Universal Trial Number (UTN)
U1111-1118-5031
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non hematologic, malignant solid tumours, excluding primary brain or spinal tumours. 258809 0
Condition category
Condition code
Cancer 258959 258959 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PG545 Powder for Reconstitution for subcutaneous Injection. Patients will be assigned to a cohort and administered between 50-500 mg of PG545 once weekly, with treatment continuing until the patient's disease progresses or they are removed from study due to a safety concern, or the study reaches its end-point. Patients will receive the same dose for the duration of the study.

It is predicted that 5 cohorts will be enrolled, though as this is a study to determine maximum tolerated dose additional cohorts may be required. The predicted dose escalation is 50 mg, 100 mg, 200 mg, 300 mg, 400 mg and 500 mg, though the dose for each cohort will be determined using Bayesian statistics and confirmed via an independant data safety monitoring board and the principal investigator.
Intervention code [1] 257738 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 259814 0
Determination of maximum tolerated dose as defined by significant dose limiting toxicity
Timepoint [1] 259814 0
Calculated using Bayesian statistics on the basis of dose limiting toxicities (DLTs) observed during the first treatment cycle (28 days) of each cohort.
Secondary outcome [1] 268615 0
Assessment of safety and tolerability of PG545 following multiple doses in subjects with advanced solid malignancies
Timepoint [1] 268615 0
Duration of treatment
Secondary outcome [2] 268616 0
To estimate pharmacokinetic parameters of PG545 and explore pharmacokinetic / pharmacodynamic relationships
Timepoint [2] 268616 0
First treatment cycle (28 days) of each cohort.
Secondary outcome [3] 268617 0
To document any antitumour activity observed with PG545
Timepoint [3] 268617 0
Duration of treatment

Eligibility
Key inclusion criteria
1. Age 18 years and older.
2. Histological or cytological documentation of non hematologic, malignant solid tumour, excluding primary brain or spinal tumours.
3. Subjects with advanced solid tumours that have failed at least one previous therapeutic regimen and either no longer are candidates for standard therapy, have no standard therapy available, or choose not to pursue standard therapy.
4. Measurable disease (at least 1 target lesion) according to RECIST 1.1.
5. Life expectancy of at least 12 weeks
6. ECOG Performance Status of 0 or 1
7. Written, signed and dated informed consent to participate in study
8. Able and willing to meet all protocol-required treatments, investigations and visits.
9. 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) than or equal to 1500 cells/microL, platelets than or equal to 100,000/microL, haemoglobin 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 prothrombin time (aPTT) and prothrombin time (PT) less = 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
1. 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.
2. Active CNS metastases. Subjects with prior CNS metastases treated by surgery and/or stereotactic irradiation are eligible providing they have no evidence of recurrent or active disease at screening. Subjects with prior CNS metastases treated with only whole brain radiation therapy are ineligible.
3. Subjects with uncontrolled diabetes.
4. History of allergy and / or hypersensitivity and / or other clinically significant adverse drug reaction to heparin or other anti-coagulant agents
5. 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
6. Concomitant use of aspirin (greater than 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 (less than or equal to 150 mg/day) and low dose prophylactic vitamin K antagonists (e.g. warfarin less than or equal to 1 mg/day) are permitted as concomitant medications
7. 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
8. Known seropositivity to the human immunodeficiency virus (HIV)
9. Women who are pregnant or breast-feeding.
10. 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).
11. Active substance abuse, including alcohol, which, in the opinion of the Investigator, risks impairing the ability of the subject to comply with the protocol
12. 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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
26/11/2010
Actual
10/01/2011
Date of last participant enrolment
Anticipated
Actual
5/08/2011
Date of last data collection
Anticipated
Actual
Sample size
Target
25
Accrual to date
Final
4
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 4862 0
Sir Charles Gairdner Hospital - Nedlands

Funding & Sponsors
Funding source category [1] 258204 0
Commercial sector/Industry
Name [1] 258204 0
Progen Pharmaceuticals Ltd
Country [1] 258204 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Progen Pharmaceuticals Ltd
Address
16 Benson Street
Toowong
Queensland
Australia 4066
Country
Australia
Secondary sponsor category [1] 257376 0
None
Name [1] 257376 0
Address [1] 257376 0
Country [1] 257376 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260187 0
Bellberry Ltd
Ethics committee address [1] 260187 0
229 Greenhill Road
Dulwich
South Australia 5065
Ethics committee country [1] 260187 0
Australia
Date submitted for ethics approval [1] 260187 0
08/09/2010
Approval date [1] 260187 0
15/11/2010
Ethics approval number [1] 260187 0
2010-09-345

Summary
Brief summary
This study looks at the safety of using a drug called PG545 in determining its maximum tolerated dose in patients with advanced tumours. In this trial, PG545 will be used for the first time in humans. We will be looking at whether taking PG545 will results in changes to chemicals produced by the body which are linked to cancer growth and spread.

Who is it for?

You can join this study if you have any advanced (metastatic/widespread), non haematologic, malignant solid tumours, except for primary brain or spinal tumours.

Trial details

All participants in this study will be assigned to a cohort and will receive PG545 at 50-500 mg once weekly until either their disease progresses, they are removed from study due to a safety concern or the study reaches its end point (estimated to be 12 months). Patients will receive the same dose for the duration of the study. Follow up assessments to determine the optimum dose of PG545, its safety and tolerability, and pharmacokinetic / pharmacodynamic profiles will be measured at the end of the first treatment cycle (28 days) and continuously throughout the treatment duration. The aim of the study is to compare these outcomes amongst all participants, and to determine the possible side effects of PG545.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32009 0
Prof Michael Millward
Address 32009 0
Sir Charles Gairdner Hospital, Nedlands, WA
Country 32009 0
Australia
Phone 32009 0
+61 (08) 6382 5100
Fax 32009 0
Email 32009 0
[email protected]
Contact person for public queries
Name 15256 0
Mr Darryn Bampton
Address 15256 0
16 Benson Street
Toowong
Queensland 4066
Country 15256 0
Australia
Phone 15256 0
+61 7 38423333
Fax 15256 0
Email 15256 0
[email protected]
Contact person for scientific queries
Name 6184 0
Mr Darryn Bampton
Address 6184 0
16 Benson Street
Toowong
Queensland 4066
Country 6184 0
Australia
Phone 6184 0
+61 7 38423333
Fax 6184 0
Email 6184 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.