Study of the Safety and Tolerability of IV Infused PG545 in Patients With Advanced Solid Tumours

An Open-label, Multi-centre Phase I Study of the Safety and Tolerability of IV Infused PG545 in Patients With Advanced Solid Tumours

This Phase Ia study aims to establish the maximum tolerated dose of once-weekly IV infused PG545 and to evaluate its safety in subjects with advanced solid tumours. 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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumours
• Intervention / Treatment: Drug: PG545

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Ltd
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >=18 years.
• Histological or cytological documentation of non hematologic, malignant solid tumour.
• Have failed at least one previous therapeutic regimen.
• LIfe expectancy >= 12 weeks.
• ECOG performance status 0 or 1.
• Written, signed and dated informed consent.
• Able and willing to meet all protocol-required treatments, investigations and visits.
• Have adequate organ function.

Exclusion Criteria:

• Clinically significant non-malignant disease.
• Active CNS metastases.
• Subjects with uncontrolled diabetes.
• History of clinically significant adverse drug reaction to heparin or other anti-coagulant agents
• Concomitant use of aspirin (> 150 mg/day), NSAIDs (except COX-2 selective inhibitors), vitamin K antagonists (other than low-dose), heparin within two weeks prior to randomisation, or other anti-platelet drugs.
• History of severe allergic, anaphylactic or other significant adverse reaction to radiographic contrast media.
• Known seropositivity to the human immunodeficiency vies (HIV)
• Women who are pregnant or breast feeding
• Women of child-bearing potential and male subjects who are partners of women of child bearing potential who are unable or unwilling to use effective means of contraception.
• Subjects who have received an investigational agent within 28 days prior to Cycle 1 Day 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PG545; Once weekly, one hour IV infusion of PG545.	Drug: PG545; PG545 will be administered once weekly, as a one hour IV infusion. Patients will be treated until they exhibit disease progression, withdraw due to poor tolerability, or the study reaches its defined end-point. This study is a dose escalation study with doses of 25 mg to 250 mg anticipated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of maximum tolerated dose (MTD) of PG545	The MTD will be determined by assessing dose limiting toxicities at the end of the first month's treatment. Dose escalation and de-escalation will continue until an MTD is identified. Each cohort of patients will receive weekly doses at a single dose level for the duration of the study.	Evaluated at the end of initial 28-day cycle

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of adverse events by cohort	Subjects will be followed for the duration of their treatment (an expected average of 12 weeks), and for four weeks post-treatment
Severity of adverse events by cohort	Subjects will be followed for the duration of their treatment (an expected average of 12 weeks), and for four weeks post-treatment
Assessment of the anti-tumour activity of PG545 using RECIST criteria	Subjects will be followed for the duration of their treatment (an expected average of 12 weeks), and then up to four weeks post-treatment

Collaborators and Investigators

• Sponsor: Zucero Pty Ltd
• Investigators: Principal Investigator: Michael Millward, MBBS, Sir Charles Gairdner Hospital

Publications and helpful links

General Publications

• Hammond E, Haynes NM, Cullinane C, Brennan TV, Bampton D, Handley P, Karoli T, Lanksheer F, Lin L, Yang Y, Dredge K. Immunomodulatory activities of pixatimod: emerging nonclinical and clinical data, and its potential utility in combination with PD-1 inhibitors. J Immunother Cancer. 2018 Jun 14;6(1):54. doi: 10.1186/s40425-018-0363-5.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: January 14, 2014
• First Submitted That Met QC Criteria: January 20, 2014
• First Posted (Estimate): January 23, 2014

Study Record Updates

• Last Update Posted (Actual): October 9, 2017
• Last Update Submitted That Met QC Criteria: October 5, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Phase I; solid tumors; antiangiogenic; tumor microenvironment; solid tumours; PG545; Progen; antimetastatic; advanced cancer patients
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: PG545102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO