An open-label, single-centre Phase I study of the safety and tolerability of PG545 in patients with advanced solid tumours
- Conditions
- Cancer - Other cancer typeson hematologic, malignant solid tumours, excluding primary brain or spinal tumours.Non hematologic, malignant solid tumours, excluding primary brain or spinal tumours.
- Registration Number
- ACTRN12611000016932
- Lead Sponsor
- Progen Pharmaceuticals Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped early
- Sex
- All
- Target Recruitment
- 25
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
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
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Determination of maximum tolerated dose as defined by significant dose limiting toxicity[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 Measures
Name Time Method Assessment of safety and tolerability of PG545 following multiple doses in subjects with advanced solid malignancies[Duration of treatment];To estimate pharmacokinetic parameters of PG545 and explore pharmacokinetic / pharmacodynamic relationships[First treatment cycle (28 days) of each cohort.];To document any antitumour activity observed with PG545[Duration of treatment]