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Trial registered on ANZCTR


Registration number
ACTRN12617001597381
Ethics application status
Approved
Date submitted
7/11/2017
Date registered
1/12/2017
Date last updated
26/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to investigate immunogenic potential of Precision Immune Stimulants-2 (PIN-2) in Patients with Advanced Solid Tumors
Scientific title
A Phase 1a study to investigate the immunogenic potential of PIN-2 administered
intravenously to patients with advanced solid tumors
Secondary ID [1] 293094 0
PIN-017-Q3
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 305031 0
Condition category
Condition code
Cancer 304354 304354 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Approximately 6-8 subjects with advanced solid tumors will be enrolled to receive one cycle of PIN-2 treatment (administered intravenously) consisting of 300 µg PIN-2, 3x per week (Day1, Day3 and Day5 of the week) for 2 weeks followed by a one week rest period. Patient who do not experience >grade 2 toxicity and in the opinion of the Investigator may benefit from a second course can receive a second course of 2 weeks treatment following a one week rest period on the same schedule as above, apart from tumor biopsies which may be performed at the discretion of the investigator. The second cycle will be given at the same dose. No dose escalation or dose reduction is permitted. No more than 2 courses will be given. PD samples will be obtained on the last day of dosing. NCI CTCAE v4.0 toxicity grading scale will be used. No intervention adherence will be assessed.
Intervention code [1] 299334 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 304041 0
The primary outcome of the study is to determine whether PIN-2 is pharmacologically active in patients with solid tumor. PIN-2 concentration is assessed by serum assay.
Timepoint [1] 304041 0
Blood for serum assay studies are collected at Screening, Day1, Day3, Day5 of week1; Day12 of week2, Day22 of week4, Day33 of week5.
Secondary outcome [1] 339610 0
Evaluation of plasma pharmacokinetics of PIN-2 in patients with solid tumors. Pharmacokinetics of PIN-2 is assessed by plasma sample. PK will be assessed by AUC.
Timepoint [1] 339610 0
Blood for PK will be collected at Screening, Day1 of week 1 and Day15 of week3.
Secondary outcome [2] 340461 0
Evaluation of immunogenic properties of PIN-2 in patients with solid tumours. This is assessed by changes in titers of anti-body to PIN-2 in serum assays.
Timepoint [2] 340461 0
Blood for serum assay studies are collected at Screening, Day1, Day3, Day5 of week1; Day12 of week2, Day22 of week4, Day33 of week5.
Secondary outcome [3] 340657 0
Characterization of safety profile of PIN-2 in patients with solid tumours. This is assessed by recording Adverse Events.
Timepoint [3] 340657 0
Adverse Events are assessed and recorded from Day1-Day5 of week1, Day8 of Week2, Day12 of week2, Day15-19 of Week3, Day22-Day26 of week4, Day29, Day31 and Day33 of week5, Day36-Day40 of week6.
Secondary outcome [4] 340661 0
Determination of whether PIN-2 induces blood (Cerebrospinal fluid-2) and tissue (tumour and/or lymph node CD 86, CD 28) markers of potential activation of the immune system in patients with solid tumours. This is assessed by changes in biomarkers (IHC) in the lymph node or tumor microenvironment or both. Safety blood samples are used for this assessment.
Timepoint [4] 340661 0
Safety blood samples are collected at Screening, Day1, Day3, Day5 of week1; Day8, Day 10, Day12 of week2, Day15-19 of week3, Day22 Day24, Day26 of week4, Day29, Day31, Day33 of week5.

Eligibility
Key inclusion criteria
1. Male or female subjects greater than equal to 18 years with a histologic diagnosis of an advanced solid tumor.
2. Women of childbearing potential and men must agree to use highly effective, double barrier contraception during the study and for 6 weeks following the final dose of PIN-2. Double barrier contraception is defined as a condom AND one other form of the following:
a. Birth control pills (The Pill)
b. Depot or injectable birth control
c. IUD (Intrauterine Device)
d. Birth control patch (e.g. Ortho Evra)
e. NuvaRing®
f. Documented evidence of surgical sterilization at least 6 months prior to the screening visit, i.e., tubal ligation or hysterectomy for women or vasectomy for men.

Biopsy: Presence of a lesion amenable to biopsy. Patients do not need to have a lesion that can be biopsied in order to be eligible for the study. The biopsy is optional to the patient.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Unable or unwilling to sign informed consent.
2. Fewer than 500 monocytes/µL as determined by CBC.
3. Fewer than 800 lymphocytes/µL as determined by CBC.
4. Any chemotherapy, immunotherapy or radiation therapy within 4 weeks prior to
treatment.
5. Expected survival <90 days.
6. Any residual toxicity >Common Terminology Criteria for Adverse Events (CTCAE) 4.0 greater than equal to grade 2.
7. Clinically active infection on antibiotic therapy within 72h prior to treatment.
8. Any medical or psychiatric condition that would, in the opinion of the investigator,
make it difficult for the subject to comply with study activities.
9. Any unstable medical or psychiatric condition.
10. Ongoing use of systemic corticosteroids or immunosuppressive agents.
11. Any immunodeficiency syndrome, including HIV infection.
12. Current brain or spinal cord metastasis.
13. Evidence of significant damage to liver (transaminases, >2.5 upper limit of normal [ULN], bilirubin>ULN), kidney (creatinine >1.25xULN), heart (MI or PCI within 6 months, unstable angina pectoris), or bone marrow (Hb<9 gm/dL, WBC <1500/µL, platelet <100,000/µL).
14. Evidence of ongoing autoimmunity from checkpoint inhibitor or other therapy (except vitiligo or endocrinopathy stable on replacement therapy)
15. Compromised or inadequate venous access
16. Pregnant or lactating women
17. Patients with tuberculosis or viral hepatitis

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable as this is a non-randomized trial
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/efficacy
Statistical methods / analysis
No preplanned statistical analysis is proposed because (a) the exploratory nature of the
study; (b) the small number of subjects; and (c) since each subject will be it’s own control
– post-treatment vs. pre-treatment to be evaluated.

Each subject will serve as his/her own control (single subject approach “SSA”).

Justification for the Choice Statistical Approach to Assess the Immune Response.
PIN-2 is a new and novel unique compound having demonstrated unique
immunomodulatory activity as determined from changes in the presence of immune
markers in the blood and immune cells in the tumor environment.
The intent of this study is to demonstrate a similar response (signals) in the human as
was observed in the mouse as well as in vitro studies with macrophages.
The SSA is a powerful research approach since it provides feedback quickly about the
effects of the treatment. The effects of treatment must be demonstrated in individual
subjects. This determines whether the treatment is working or not and permits the
observation of day to day changes. The SSA permits the investigator to draw
conclusions regarding the factors that control the dependent variable. To be an
acceptable evaluation of the treatment, the results for each subject must demonstrate
intra and inter subject replication.

Immunogenicity, Pharmacokinetics, Safety:
Analyses will be quantitative and will be focused on changes comparing post (following
administration of PIN-2) versus pre (baseline) of the immune response (changes in
immune cell population in the blood, changes in blood biomarkers and changes in
biomarkers (IHC) in the lymph node or tumor microenvironment or both) pre and post
administration of PIN-2 will be determined by the delta looking for the signal and trend.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 9175 0
Linear Clinical Research - Nedlands
Recruitment hospital [2] 12011 0
Ashford Cancer Centre: Adelaide Cancer Centre - Kurralta Park
Recruitment postcode(s) [1] 24168 0
5037 - Kurralta Park
Recruitment postcode(s) [2] 17691 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 297720 0
Commercial sector/Industry
Name [1] 297720 0
PIN Pharma Pty Ltd
Address [1] 297720 0
58 Gipps Street
Collingwood, VIC 3066
Country [1] 297720 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
PIN Pharma Pty Ltd
Address
58 Gipps Street
Collingwood, VIC 3066
Country
Australia
Secondary sponsor category [1] 296746 0
None
Name [1] 296746 0
Address [1] 296746 0
Country [1] 296746 0
Other collaborator category [1] 279761 0
Commercial sector/Industry
Name [1] 279761 0
Novotech (Australia) Pty Limited
Address [1] 279761 0
Level 3, 235 Pyrmont Street
Pyrmont, New South Wales, 2009
Country [1] 279761 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298786 0
Bellberry Limited
Ethics committee address [1] 298786 0
129 Glen Osmond Road
Eastwood, South Australia 5063
Ethics committee country [1] 298786 0
Australia
Date submitted for ethics approval [1] 298786 0
20/09/2017
Approval date [1] 298786 0
02/11/2017
Ethics approval number [1] 298786 0
2017-09-686

Summary
Brief summary
The purpose of this study is to investigate whether a new drug called PIN-2 is safe and activates the immune system in patients with advanced solid tumours.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above and have a histologic diagnosis of an advanced solid tumor.

Study details
All participants in this study will receive one cycle of chemotherapy treatment with the drug, PIN-2 (Precision Immune Stimulants). PIN-2 will be administered intravenously (i.e. directly into the vein) 3 x per week for 2 weeks followed by a one week rest period. If tolerated and deemed beneficial, a second identical course may be administered. No more than 2 courses in total will be given.

Participants will be regularly monitored for safety, and asked to provide a number of blood samples across a 5 week period to assess how the body processes and responds to the drug. Tissue samples (tumor and/or lymph node) will also be obtained, if possible, at pre-treatment and again at the conclusion of each treatment cycle for evaluation. Patients who are eligible for and agree to participate in the biopsy will have tumor biopsy prior to treatment and at week 3.

This study will help find new methods of treatment for the patients with solid tumors.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78226 0
Prof Michael Millward
Address 78226 0
SCGH, B Block, Hospital Avenue,
Nedlands, 6009, WA, Australia
Country 78226 0
Australia
Phone 78226 0
+61 8 9346 2098
Fax 78226 0
Email 78226 0
michael.millward@uwa.edu.au
Contact person for public queries
Name 78227 0
Dr Colin Bier
Address 78227 0
PIN Pharma Pty Ltd
58 Gipps Street
Collingwood, VIC 3066
Country 78227 0
Australia
Phone 78227 0
+61 3 9419 7607
Fax 78227 0
Email 78227 0
cbier@pinpharma.com
Contact person for scientific queries
Name 78228 0
Dr Colin Bier
Address 78228 0
PIN Pharma Pty Ltd
58 Gipps Street
Collingwood, VIC 3066
Country 78228 0
Australia
Phone 78228 0
+61 3 9419 7607
Fax 78228 0
Email 78228 0
cbier@pinpharma.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary