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Trial registered on ANZCTR


Registration number
ACTRN12610000733077
Ethics application status
Approved
Date submitted
18/08/2010
Date registered
3/09/2010
Date last updated
23/04/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
PAT-SM6 in Patients with Recurrent In-Transit Cutaneous Melanoma
Scientific title
A Single Dose, Dose Escalating, Phase I Clinical Trial to Determine the Safety of a Single Dose of PAT-SM6 Monoclonal Antibody in Patients with Recurrent In-Transit Cutaneous Melanoma
Secondary ID [1] 252579 0
None
Universal Trial Number (UTN)
Trial acronym
PATCT-SM6-01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent in-transit cutaneous melanoma 257993 0
Condition category
Condition code
Cancer 258158 258158 0 0
Malignant melanoma
Skin 258241 258241 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single dose of Human anti-GRP78 Immunoglobulin M (IgM) monoclonal antibody PAT-SM6 via intravenous infusion over 60 minutes. The initial cohort of 3 patients will receive 0.15mg/kg, the second cohort will receive 0.3mg/kg and the final cohort will receive 0.6mg/kg.
Intervention code [1] 257042 0
Treatment: Drugs
Comparator / control treatment
NA
Control group
Uncontrolled

Outcomes
Primary outcome [1] 259018 0
Safety - Evaluated using the United States (US) National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0, based on recorded adverse events, and by changes from baseline in the patient?s physical examinations, vital signs, performance status and clinical laboratory assessments.
Timepoint [1] 259018 0
Continuously throughout the study until Exit Visit on Day 36
Secondary outcome [1] 265251 0
Describe the pharmacokinetics of PAT-SM6
Timepoint [1] 265251 0
Before the PAT-SM6 infusion, immediately post-infusion, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-infusion. Additional blood will be collected at 48, and 72 hours post-infusion and Day 4 (prior to tumour biopsy), Day 8 and Day 15 Visits from baseline.
Secondary outcome [2] 265252 0
Screen for the development of antibodies against PAT-SM6 (immunogenicity).
Timepoint [2] 265252 0
Day 1, Day 8, Day 15, Day 22, Day 36 from baseline.
Secondary outcome [3] 265253 0
Explore the antitumor activity of PAT-SM6 via clinical assessment and clinical photography (where applicable).
Timepoint [3] 265253 0
Day 4 and throughout the study until Exit Visit on Day 36.
Secondary outcome [4] 265254 0
Assess the pharmacodynamic effect(s) of PAT-SM6 in patient tumour samples and to identify potential predictors (biomarkers) of therapeutic efficacy and/or safety.
Timepoint [4] 265254 0
Day 4 and throughout the study until Exit Visit on Day 36.

Eligibility
Key inclusion criteria
1. The patient has recurrent in-transit cutaneous melanoma based on diagnosis by cytology or histology. The patient may or may not have asymptomatic distant metastatic disease limited to Stage M1a.
2. The patient is willing and able to provide a pre- and post-treatment tumour biopsy.
3. The patient has an Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0, 1 or 2 at study entry.
4. The patient has provided written informed consent.
5. The patient is age 18 years or older.
6. The patient has a life expectancy of > 3 months.
7. The patient has adequate hematologic function, as defined by: - an absolute neutrophil count >= 1500/mm3 - a platelet count >= 100,000/mm3
8. The patient has a haemoglobin level >9 g/dL.
9. The patient has adequate hepatic function, as defined by: - a total bilirubin level <= the upper limit of normal (ULN) unless due to congenital Gilbert’s syndrome - aspartate transaminase (AST) and alanine transaminase (ALT) levels <= 2.5 x the ULN
10. The patient has adequate renal function, with calculated creatinine clearance (using Cockcroft Gault formula) of >50 mL/min and 0 to 1+ proteinuria.
11. The patient uses effective contraception (per the institutional standard), if procreative potential exists.
12. The patient has adequately recovered from any recent therapy, including surgery, chemotherapy, and radiation therapy.
13. The patient is accessible for treatment and follow-up at the participating centre.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. The patient has metastatic disease at Stage M1b (lung metastases with normal LDH of <=ULN) or M1c (other distant metastases or any distant metastases with elevated LDH of >ULN). 2. The patient has received chemotherapy or therapeutic radiotherapy within 28 days prior to the first dose of study medication or has ongoing side effects >= Common Terminology Criteria for Adverse Events (CTCAE) (Version 4.0) Grade 2 due to agents administered more than 28 days earlier. 3. Immunosuppressive therapy including corticosteroids within four weeks of screening; 4. The patient has uncontrolled intercurrent illness including, but not limited to: - ongoing or active infection requiring parenteral antibiotics, - symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease), - unstable angina pectoris, angioplasty, stenting, or myocardial infarction six months prior to the first dose of study medication, - uncontrolled hypertension (systolic blood pressure >160 mmHg, diastolic blood pressure >100 mmHg, found on two consecutive measurements separated by a one week period despite adequate medical support), - clinically significant cardiac arrhythmia including but not limited to: multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment, CTCAE, Version 4.0, Grade 3, or asymptomatic sustained ventricular tachycardia, - uncontrolled diabetes, - psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements, 5. The patient has known human immunodeficiency virus positivity. 6. The patient has had a major surgical procedure or a significant traumatic injury within 28 days prior to treatment. 7. The patient is currently or has recently used (within 28 days prior to) a thrombolytic agent. 8. The patient is currently using full-dose warfarin (an exception is low-dose warfarin to maintain patency of pre-existing, permanent, indwelling intravenous catheters; for patients receiving warfarin, the international normalised ratio [INR] should be <1.5). A patient requiring heparin is excluded. A patient receiving antiplatelet agents such as non-steroidal anti-inflammatory drugs including aspirin, clopidogrel and dipyramidole is excluded. 9. Known hemorrhagic diathesis or active bleeding disorder. 10. The patient has any condition, which in the Investigator’s opinion, puts the patient at significant risk, could confound study results, or may interfere with the patient’s participation in the study. 11. The patient has received an Investigational Product within 30 days prior to dosing, or five half-lives of the drug whichever is longer. 12. The patient has a QTc interval of greater than 450 ms (males) and 470 ms (females).

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
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)
SA
Recruitment postcode(s) [1] 3160 0
5000

Funding & Sponsors
Funding source category [1] 257489 0
Commercial sector/Industry
Name [1] 257489 0
Patrys Limited
Address [1] 257489 0
614/343 Little Collins St, Melbourne VIC 3000
Country [1] 257489 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Patrys Limited
Address
614/343 Little Collins St, Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 256725 0
None
Name [1] 256725 0
Address [1] 256725 0
Country [1] 256725 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259516 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 259516 0
The Royal Adelaide Hospital Research Ethics Committee
Level 3, Hanson Institute
IMVS Building
North Terrace
ADELAIDE SA 5000
Ethics committee country [1] 259516 0
Australia
Date submitted for ethics approval [1] 259516 0
Approval date [1] 259516 0
27/07/2010
Ethics approval number [1] 259516 0

Summary
Brief summary
This study looks at the effectiveness and safety of a single dose of PAT-SM6 in treating people with melanoma of the skin.
Who is it for?
You may be able to join this study if you have locally recurring cutaneous (skin) melanoma. You must not have received chemotherapy or therapeutic radiotherapy in the previous 28 days. You will be required to have a biopsy sample of the melanoma prior to receiving study medication.
Trial details:
Participants will all receive a single dose of human anti-GRP78 IgM monoclonal antibody PAT-SM6 via intravenous infusion over 60 minutes, at varying doses. They will return to the site on day 4 for another biopsy of the melanoma/surgery. Patients will remain on study for 5 weeks. The study aims to monitor the safety and effectiveness of treatment.
What is PAT-SM6?
PAT-SM6 is different to other antibodies on the market for cancer because it a naturally-occurring human molecule. It fights tumours by fixing on to specific targets on cancerous cells and killing them.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31533 0
Address 31533 0
Country 31533 0
Phone 31533 0
Fax 31533 0
Email 31533 0
Contact person for public queries
Name 14780 0
Lynn Hawkes
Address 14780 0
Cancer Clinical Trials Unit
RAH Cancer Centre
Professor of Medicine, University of Adelaide
MDP 11, Level 4, East Wing
North Terrace, Adelaide SA 5000
Country 14780 0
Australia
Phone 14780 0
+61 8 8222 4157
Fax 14780 0
Email 14780 0
lynn.hawkes@health.sa.gov.au
Contact person for scientific queries
Name 5708 0
Professor Michael P. Brown
Address 5708 0
Director of Cancer Clinical Trials
RAH Cancer Centre
Professor of Medicine, University of Adelaide
MDP 11, Level 4, East Wing
North Terrace, Adelaide SA 5000
Country 5708 0
Australia
Phone 5708 0
+61 8 8222 4157
Fax 5708 0
Email 5708 0
Michael.Brown@health.sa.gov.au

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