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Trial registered on ANZCTR


Registration number
ACTRN12619001033134
Ethics application status
Approved
Date submitted
5/07/2019
Date registered
18/07/2019
Date last updated
18/07/2019
Date data sharing statement initially provided
18/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Bio-distribution evaluations of MUC-1 specific targeted immune-radiotherapy for advanced pancreatic adenocarcinoma: a first pilot human study.
Scientific title
Bio-distribution evaluations of MUC-1 specific targeted immune-radiotherapy for advanced pancreatic adenocarcinoma: a first pilot human study.
Secondary ID [1] 298656 0
n/a
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic Cancer 313552 0
Condition category
Condition code
Cancer 311986 311986 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
20 patients with either locally advanced or metastasized Pancreatic Ductal Adenocarcinoma (PDAC), who are referred for Endoscopic Ultrasound (EUS) Fine Needle Acquisition (FNA), will be approached for the study. Staging will include CT scans of the chest, abdomen and pelvis, and a diagnostic 18FDG PET scan. Based on the probable 80% positive rate for the glycoprotein Mucin-1 (MUC-1), it is expected that 15-16 patients who have MUC-1 positive PDAC will be recruited for the study.

In addition to histological evaluation of the EUS-guided biopsy, MUC-1 receptor staining using Immunohistochemistry techniques will be done at the Department of Pathology, Royal Adelaide Hospital (RAH). Only patients who have confirmed PDAC with positive MUC-1 stain will be recruited to the next study phase. In all patients, full blood count, kidney and liver function, and urinary dipstick for proteinuria/hematuria tests will be performed, including staging.

The first 10 recruited patients will undergo immediate bio-distribution evaluation with 99mTc-C595 conjugates planar and SPECT/CT scanning, within 2 weeks after the biopsy. This is to ensure that the study will not cause any unnecessary delay to chemotherapy. On the study day, the patient will be evaluated with one planar and SPECT/CT scan, up to 4 hours after an IV injection of 99mTc-C595 conjugate, prepared by the Department of Nuclear Medicine, RAH. For 111 MBq of 99mTc-C595, the dose is ~1.2 mSv. Over the 4 hours, vital signs (temperature, blood pressure, heart rate and pulse) will be taken every 15 minutes. Providing the vital signs are normal, the patients will be discharged home after the SPECT/CT scan.

Providing that the 99mTc-C595 conjugate distribution demonstrates specific localization of C595 Mab to the primary and secondary lesions of pancreatic cancer, the subsequent recruited patients (n= 5 or 6 subjects) will be evaluated with 111In-C595 injection to ensure that there are no delayed anomalous organ uptake, and confirm ongoing binding to the pancreatic cancer lesion(s). For 80 MBq of 111In-C595, the dose is ~18 mSv. In these studies, the patients will undergo one SPECT/CT scan at 4 hours, one at 24 hours, and one up to Day 4 after IV injection of 111In-C595. Again, vital signs (temperature, blood pressure, heart rate and pulse) will be taken every 15 minutes over the first 3 hours of injection. If the 99mTc-C595 conjugate distribution study fails to demonstrate specific localization of C595 Mab, the study will be terminated at this point.

Both 99mTc-C595 and 111In-C595 are considered interventions for the study. This is a proof-of-concept study to evaluate the specific bio-distribution of the two C595 labelled radionuclide markers (99mTc and 111In immunoconjugates) to pancreatic cancer cells in patients who have advanced MUC1-positive pancreatic carcinoma.

In111 and Tc99m-C595 conjugates will be manufactured at the RAH Nuclear Medicine Department Radiopharmacy Hot Laboratory. All manufacturing processes will be undertaken in a lead lined Clas II biological safety cabinet in the laboratory. Production will be undertaken by a radio-chemist/pharmacist. Both injections will be administered by the investigator of the study.
Intervention code [1] 314918 0
Diagnosis / Prognosis
Comparator / control treatment
No control group. Both 99mTc-C595 and 111In-C595 are considered interventions for the study, as the aim is to evaluate the specific bio-distribution of the two c595-labelled radionuclide markers to pancreatic cancer cells.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320626 0
To observe bio-distribution of 99mTc-C595 conjugates on planar and SPECT/CT scans, and compare with diagnostic staging CT and 18FDG PET scans.
Timepoint [1] 320626 0
Imaging of bio-distribution of 99mTc-C595 will be captured via SPECT/CT scans 4 hours after injection.
Outcomes of SPECT/CT scans will be assessed within 2 days after imaging.
Primary outcome [2] 320683 0
To observe bio-distribution of 111In-C595 conjugates on planar and SPECT/CT scans, and compare with diagnostic staging CT and 18FDG PET scans.
Timepoint [2] 320683 0
Imaging of bio-distribution of 111In-C595 will be captured via SPECT/CT scans at 4 hours, 24 hours, and up to Day 4 after injection.
Outcomes of SPECT/CT scans will be assessed within 2 days after imaging.
Secondary outcome [1] 372256 0
Any adverse effects, defined as any undersirable experience occurring to a subject during the study. This may include:

(i) Intraprocedural adverse events from EUS-guided biopsy: bleeding (intraparietal or retroperitoneal) or perforation.
(ii) Post-procedural adverse events: clinical relevant bleeding (drop >2g/dl of hemoglobin or need for blood transfusion); perforation; post-EUS pancreatitis (abdominal pain with three times serum amylase/lipase elevation or pancreatitis at imaging); infection.
(iii) Adverse events from Mab intravenous injection: nausea, vomiting, and skin irritation at injection site.
Timepoint [1] 372256 0
All participants will be monitored for post procedural adverse events within 72 hours after EUS. Following Mab IV injection, the participant will be monitored over 4 hours, with vital signs taken every 15 minutes.
The participants medical records will be checked over the next 12 months.

Eligibility
Key inclusion criteria
(i) Subjects aged 18 years or older, and able to provide informed consent and expected to survive for >3 months.
(ii) Histological proven pancreatic ductal carcinoma with positive MUC-1.
(iii) Karnofsky performance status > 70%.
(iv) Neutrophil count > f 1.5 x 10^9/L, platelet counts of greather than/equal to 100 x 10^9/L; Hb greater than/equal to 9.0g/dL (90 g/L) without transfusion or erythropoietin support within 2 weeks prior to screening, total bilirubin level less than/equal to 1.5 x ULN, AST and ALT levels more than 2 times the upper limit of normal and GFR greater than/equal to 60 mL/min.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(i) Known renal conditions: glomerulonephritis; IgA nephropathy, acute renal failure, current CNS metastases.
(ii) Known mouse product allergy.
(iii) Chemo or immunotherapy within 4 weeks prior or radiotherapy within 2 weeks of Target Radio-Immunotherapy.
(iv) Liver disease with liver enzyme greater than 3 times of normal.
(v) Pregnancy or lactation.

Study design
Purpose of the study
Diagnosis
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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Based on the probable 80% positive rate for MUC-1, it is expected that 15-16 patients who have MUC-1 positive PDAC will be recruited for the study. As this is an explorative pilot study, no power calculations to determine the sample size can be done.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2019
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 14141 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 26953 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 303196 0
Hospital
Name [1] 303196 0
Royal Adelaide Hospital 2019 Clinical Project Grant
Country [1] 303196 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Port Road, Adelaide, South Australia, 5000
Country
Australia
Secondary sponsor category [1] 303210 0
None
Name [1] 303210 0
Address [1] 303210 0
Country [1] 303210 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303757 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 303757 0
Ethics committee country [1] 303757 0
Australia
Date submitted for ethics approval [1] 303757 0
Approval date [1] 303757 0
15/05/2019
Ethics approval number [1] 303757 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94690 0
A/Prof Nam Nguyen
Address 94690 0
Royal Adelaide Hospital, Port Road, Adelaide, South Australia, 5000
Country 94690 0
Australia
Phone 94690 0
+61 8 7074 2189
Fax 94690 0
+61 8 7074 6192
Email 94690 0
quocnam.nguyen@sa.gov.au
Contact person for public queries
Name 94691 0
Romina Safaeian
Address 94691 0
Royal Adelaide Hospital, Port Road, Adelaide, South Australia, 5000
Country 94691 0
Australia
Phone 94691 0
+61 8 7074 2189
Fax 94691 0
+61 8 7074 6192
Email 94691 0
romina.safaeian@sa.gov.au
Contact person for scientific queries
Name 94692 0
Romina Safaeian
Address 94692 0
Royal Adelaide Hospital, Port Road, Adelaide, South Australia, 5000
Country 94692 0
Australia
Phone 94692 0
+61 8 7074 2189
Fax 94692 0
+61 8 7074 6192
Email 94692 0
romina.safaeian@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.