The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000088145
Ethics application status
Approved
Date submitted
5/12/2018
Date registered
22/01/2019
Date last updated
28/01/2020
Date data sharing statement initially provided
22/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Prospective trial comparing nanoparticle-magnetic resonance lymphography and 68Ga-PSMA positron emission tomography in nodal staging of prostate cancer
Scientific title
Prospective evaluation of lymph node imaging for the nodal staging of prostate cancer with a high risk of lymph node metastases: A prospective cohort study to determine the concordance between two imaging modalities, “Combidex” Nanoparticle-Magnetic Resonance Lymphography (Nano MRL) and 68Ga-PSMA positron emission tomography (PET)
Secondary ID [1] 296801 0
MAGNIFI Trial
Universal Trial Number (UTN)
Trial acronym
MAGNIFI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer 310691 0
Condition category
Condition code
Cancer 309390 309390 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. Men diagnosed with prostate cancer are referred to a participating urologist for a radical prostatectomy
2. The patients are consented to the study by the urologist or research assistants following fulfilment of the inclusion criteria
3. The patient is referred to a Department of Nuclear Medicine (St Vincent's Hospital Sydney or The Wesley Hospital Brisbane) where a 68Ga-PSMA (68Gallium-Prostate Specific Membrane Antigen Positron Emission Tomography: using a radioactive labelled antigen, positron emission tomography can detect lymph node metastases) PET Scan is performed
5. On the return visit, “Combidex” is administered at 2.6 mg Fe/kg intravenously after dilution in 300mls of normal saline to the patient by trained and qualified nursing staff and the patient is referred for a MRI scan (Medscan Barangaroo or The Wesley Hospital Brisbane) - this will constitute the 'MRL scan' (Nanoparticle-magnetic resonance lymphography (Combidex Nano MRL): using nanoparticle iron oxide particles as a contrast agent, magnetic resonance imaging can detect lymph node metastases at 2mm in size)
6. Radiologist and Urologist annotate suspect lymph nodes using the Pelvic Lymph Node Diagnostic Template and assign index of suspicion to each area
7. Patient undergoes radical prostatectomy including the removal of lymph nodes 7-10 days following Combidex nano-MRL
8. The prostate and the lymph nodes are sent to histology for reporting
9. Analysis:
a. Histology Vs Nano-MRL
b. Histology Vs Ga68 PSMA PET
c. Histology Vs Nano-MRL Vs Ga68 PSMA PET
10. Repeat Ga68 PSMA and Nano-MRL if not concordant with Histology within 6-8 weeks of surgery
11. Follow up Visits: The participant will have clinical follow up reviews as part of their care at 6 weeks, 3 months, 6 months, 12 months and 24 months
12. Participant will complete the Expanded Prostate Cancer Index Composite (EPIC) survey at baseline (prior to surgery), 6 weeks, 3 months, 6 months, 1 years and then yearly for a minimum of 5 years).
Intervention code [1] 313093 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 308347 0
We will compare ‘packet concordance rate’ between histology and MR Lymphography using a MRA arterial map (that can be acquired at the MRL) to locate the position of the lymph node, the 68Ga PSMA PET SCAN plus a combined evaluation, and histology.
Timepoint [1] 308347 0
When histopathology of lymph node dissection is available.
Secondary outcome [1] 365553 0
As part of initial longitudinal analyses quality of life (as measured using EORTC-QLQ-C30) will be evaluated using one-way ANOVA.
Timepoint [1] 365553 0
As follow-up data becomes available, continuous reanalysis will occur. Initially at 3 months, then 6 months then 12 months and yearly from then until lost to follow-up or death.

Eligibility
Key inclusion criteria
• Male, aged 18 years or over
• Confirmed adenocarcinoma of prostate and at least clinical stage T3A and/or Gleason sum greater than or equal to 4+3=7, or preoperative PSA equals 15 ng/ml and planned radical prostatectomy
• Suspected lymph node involvement pre- radical prostatectomy based on Briganti nomogram greater than or equal to 10%.
• Suitable for radical prostatectomy and pelvic lymph node dissection, as per institutional guidelines and not yet treated pre-prostatectomy
• Subject is able to understand and willing to sign the participant information statement and consent form
• Subject is expected to remain available for 24 months of clinic visits
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
• Past history any other type of cancer (except skin cancer).
• Previous treatment for prostate cancer (surgery, radiotherapy, chemotherapy, hormone androgen deprivation therapy)
• Proven bony metastatic disease, visceral metastases or lymph node metastases above the level of the aortic bifurcation
• Previous surgery in pelvis (e.g. bilateral hip replacement) that limit the extent of pelvic lymph node dissection
• Patients who refuse radical prostatectomy or pelvic lymph node dissection
• Patients who refuse to join the trial or are unable to consent
• Patients not being considered for further therapy
• Patient has absolute contra-indications to undergoing MRI scanning
• Patients who cannot lie still for at least 60 to 75 minutes or comply with imaging
• Subject has medical conditions that would limit study participation (per physician discretion)
• Subject is enrolled in one or more concurrent studies that would confound the study results of this study as determined by the study investigators
• Subject has a limited life expectancy that would not allow completion of the 24 month visits

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
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
We will recruit 120 patients. Considering that each patient has 6 packets (a lump of fat containing lymph nodes) on average, we will be comparing 720 packets in total. This number will give 90% power to detect a 10% or less discordance between final histology analysis and the combined imaging modalities consensus.

We will compare ‘packet concordance rate’ between histology and MR Lymphography using a MRA arterial map (that can be acquired at the MRL) to locate the position of the lymph node, the 68Ga PSMA PET SCAN plus a combined evaluation, and histology. We will calculate the CONCORDANCE rate for positive nodes in each packet with their corresponding region on imaging, both against each individual imaging modality and against a summed score from both imaging techniques. Sensitivity, specificity, negative predictive values (NPVs), and positive predictive values (PPVs) will be reported. The maximum likelihood estimates (MLEs) of PPV and NPV will be calculated from the MLEs of the sensitivity, specificity, and prevalence rate. Hierarchical modelling will be used to test for concordance between matched results from each packet.

Recruitment
Recruitment status
Recruiting
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)
NSW,QLD
Recruitment hospital [1] 12656 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 12657 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 12658 0
The Wesley Hospital - Auchenflower
Recruitment postcode(s) [1] 25078 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 25079 0
4066 - Auchenflower

Funding & Sponsors
Funding source category [1] 301376 0
Charities/Societies/Foundations
Name [1] 301376 0
Paul Ramsay Foundation
Address [1] 301376 0
Paul Ramsay Foundation
Level 9, 154 Pacific Hwy
St Leonards NSW 2065
Australia
Country [1] 301376 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Garvan Institute of Medical Research
Address
384 Victoria St
DARLINGHURST NSW 2010
Country
Australia
Secondary sponsor category [1] 301044 0
None
Name [1] 301044 0
Address [1] 301044 0
Country [1] 301044 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302114 0
St Vincent's Hospital Sydney Human Research Ethics Committee
Ethics committee address [1] 302114 0
97-105 Boundary Street
Darlinghurst NSW 2010
Ethics committee country [1] 302114 0
Australia
Date submitted for ethics approval [1] 302114 0
12/11/2015
Approval date [1] 302114 0
12/01/2016
Ethics approval number [1] 302114 0
HREC/15/SVH/402

Summary
Brief summary
The purpose of this study is to determine if new imaging technologies are a valid and accurate method of detecting lymph node metastases.

Who is it for?

You may be eligible for this study if you are an adult who has been diagnosed with prostate cancer.

Study details

All participants will have 2 specialised imaging scans (68Ga-PSMA PET and nano-MRL) prior to a prostatectomy and lymph node dissection.

It is hoped that this research will help determine if these two imaging tests are useful in providing accurate but non-invasive methods of diagnosing metastatic prostate cancer. Thus guiding better targeted treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89158 0
Prof Phillip Stricker
Address 89158 0
St Vincent’s Hospital, Sydney
St Vincent’s Prostate Cancer Centre
Suite 1001, Lvl 10, St Vincent’s Clinic,
408 Victoria Street
Darlinghurst NSW 2010
Country 89158 0
Australia
Phone 89158 0
+61,02,83826971
Fax 89158 0
+61,02,83826972
Email 89158 0
pstricker@stvincents.com.au
Contact person for public queries
Name 89159 0
Mr Thomas Cusick
Address 89159 0
The Kinghorn Cancer Centre 370 Victoria Street, Darlinghurst NSW 2010
Country 89159 0
Australia
Phone 89159 0
+610293555795
Fax 89159 0
Email 89159 0
t.cusick@garvan.org.au
Contact person for scientific queries
Name 89160 0
Prof Phillip Stricker
Address 89160 0
St Vincent’s Hospital, Sydney St Vincent’s Prostate Cancer Centre Suite 1001, Lvl 10, St Vincent’s Clinic, 408 Victoria Street Darlinghurst NSW 2010
Country 89160 0
Australia
Phone 89160 0
+610283826971
Fax 89160 0
Email 89160 0
pstricker@stvincents.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data will be de-identified and pooled to ensure anonymity of participants.
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 615 0
Ethical approval
Citation [1] 615 0
Link [1] 615 0
Email [1] 615 0
t.cusick@garvan.org.au
Other [1] 615 0
Type [2] 616 0
Study protocol
Citation [2] 616 0
Link [2] 616 0
Email [2] 616 0
t.cusick@garvan.org.au
Other [2] 616 0
Type [3] 6628 0
Informed consent form
Citation [3] 6628 0
Link [3] 6628 0
Email [3] 6628 0
t.cusick@garvan.org.au
Other [3] 6628 0
Summary results
No Results