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Trial registered on ANZCTR


Registration number
ACTRN12618001552279
Ethics application status
Approved
Date submitted
3/07/2018
Date registered
17/09/2018
Date last updated
17/09/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Radionuclide therapy using 177Lu-PSMA: a pilot study in men with castrate-resistant prostate cancer (LuPSMA trial)
Scientific title
Radionuclide therapy using 177Lu-PSMA: a pilot study in men with castrate-resistant prostate cancer (LuPSMA trial)
Secondary ID [1] 295415 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
castrate-resistant prostate cancer 308652 0
Condition category
Condition code
Cancer 307592 307592 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study is designed as a prospective, open label, single arm non-randomised pilot study in men with prostate specific membrane antigen (PSMA) expressing castration-resistant progressive prostate cancer. Progression has to be within the preceding 6 months based on radiology and or symptomatic progression.

Participants will be screened to determine the suitability of participating in the study. During the screening visit(s) they will asked to sign consent, provide medical history, height, weight, physical assessment, undergo a 68Ga-PSMA PET/CT scan, FDG PET/CT scan, Isotope bone scan, contrast-enhanced CT (chest/ abdomen/ pelvis) scan, blood tests and complete questionnaires.

If the participant is suitable to the study they will receive a single IV injection of 177 Lu-PSMA on day 0. The dose given is calculated by the doctor based on the participant's weight and volume of disease. Dose will vary between individuals with a dosage regimen of IV 4-8 GBq of 177Lu-PSMA activity, 50 micrograms PSMA per GBq. Participants will be monitored during and post injection by clinical trial team members. Blood samples will be taken after infusion and approximately 4 hours post administration a 177Lu-PSMA SPECT/CT will occur. Follow up post therapy imagining will occur at approximately 24 and 72 hours post injection with a 177Lu-PSMA SPECT/CT.

Participants will be followed up on day 14 and 28 to assess the routine blood results and complete questionnaires. A full cycle comprises of a 42 day cycle and participants can receive up to four cycles of therapeutic 177Lu-PSMA. Participants will be routinely followed up with treating doctor before each cycle to assess benefit of treatment and adherence to study. For Cycles 2-4, participants follow the same schedule of events with the exemption that one a single time-point 177Lu-PSMA SPECT/CT will performed 1 day after administration of 177 Lu-PSMA .
Intervention code [1] 301722 0
Treatment: Drugs
Comparator / control treatment
'No control group'
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306569 0
To determine the toxicity profile of 177Lu PSMA graded by CTCAE version 4.03
Timepoint [1] 306569 0
The assessments will occur at baseline, after one cycle of treatment and at the end of each cycle thereafter.
Primary outcome [2] 306570 0
To document indicators of anti-cancer efficacy using 177Lu-PSMA using surrogate measures from medical imaging
Timepoint [2] 306570 0
Radiologic response 3 months post completion of therapy (RECIST v1.1): complete response, partial response, stable disease, progressive disease

Molecular imaging response post dose 2 and 3 months post completion of therapy: complete metabolic response, partial metabolic response, stable metabolic disease, progressive metabolic disease.
Primary outcome [3] 307456 0
To document indicators of anti-cancer efficacy using 177Lu-PSMA using surrogate measures using serum PSA.
Timepoint [3] 307456 0
Serum PSA response 3 months post completion of therapy
Secondary outcome [1] 348912 0
To investigate the normal tissue bio-distribution of repeated doses of 177Lu PSMA using medical imaging tools (Isotope bone scan, Contrast enhanced CT, PSMA PET/CT, FDP PET/CT and 177Lu PSMA SPECT imaging).
Timepoint [1] 348912 0
The assessments will occur at baseline, after one cycle of treatment and at the end of each cycle thereafter. Normal tissue dosimetry expressed in Gy.
Secondary outcome [2] 348913 0
To document the progression-free rates following therapy
Timepoint [2] 348913 0
Progression-free rates are determined from date of commencement of PSMA therapy to documents progression. A participant will be followed up indefinitely or until the participant asks to be withdrawn from the study
Secondary outcome [3] 348914 0
To document changes in serum PSMA during therapy
Timepoint [3] 348914 0
Serum PSMA response 3 months following completion of therapy will be compared to the assessment at pre-treatment and during treatment (taken at the start of each cycle, day 14 and day 28 of each cycle).

Eligibility
Key inclusion criteria
1. Age 18 years and older
2. Pathologically confirmed prostate adenocarcinoma
3. Castration-resistant metastatic disease,
4. Prior treatment with Abiraterone, Enzalutamide or both (unless contraindicated, medically unsuitable or patient refuses)
5. Prior Taxane-based chemotherapy (unless contraindicated, medically unsuitable or patient refuses)
6. Documented prostate cancer progression within last 12 months as defined by PSA progression (minimum of three rising PSA levels with an interval of greater than 1 week between each determination OR radiographic progression (soft tissue disease by RECIST v1.1 criteria or two or more documented new bone lesions on a bone scan )
7. PSMA PET/CT demonstrating uptake intensity significantly greater than liver at sites of disease
8. Surgically or medically castrated, with testosterone levels of less than 50 ng/dL (less than 2.0 nM). If the patient is being treated with LHRH agonists (patient who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and must be continued throughout the study.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of less than 2
10. Life expectancy greater than 12 weeks.
11. Written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Estimated GFR less than 40 ml/min
2. Platelet count less than 75,000 x109 /L
3. Neutrophil count less than 1.5 x109 /L
4. Hb less than 9.0 g/dL
5. Albumin at least 25
6. Hydronephrosis with ureteric obstruction
7. Concomitant nephrotoxic drugs (e.g. aminoglycosides)
8. FDG PET/CT demonstrating sites of major discordant disease (i.e. FDG + PSMA-)
9. Recent radiotherapy (within 6 weeks) to sole sites of assessable disease
10. Uncontrolled inter-current illness that would limit compliance with study protocols

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
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
Primary end-points:
1. Descriptive statistics will be used to document change in pain scores, QOL scores, PSA response and imaging disease response at 3 months following completion of therapy compared to baseline scores along with 95% confidence interval.
a. For PSA, the percentage of patients with 50% decline from baseline will be described as per Prostate Cancer Working Group (PCWG2)
2. The proportion of patients who suffer grade 1,2 3 or 4 toxicity will be provided along with its 95% confidence interval.

Secondary end-points:
1. Mean absorbed dose (Gy) estimated in in normal tissues and tumour will be recorded along with 95% confidence interval.
2. Kaplan-Meier methods will be used to describe progression free and overall survival at 6 and 12 months, defined from the date of start of treatment. This will be estimated from the Kaplan-Meier curve along with the corresponding 95% confidence intervals.

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)
NSW
Recruitment hospital [1] 11303 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 23201 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 300003 0
Hospital
Name [1] 300003 0
St Vincent’s Prostate Cancer Centre
Address [1] 300003 0
Suite 1001, Level 10
St Vincent’s Clinic
438 Victoria Street
Darlinghurst
NSW, 2010
Country [1] 300003 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital
Address
390 Victoria St
Darlinghurst
NSW, 2010
Country
Australia
Secondary sponsor category [1] 299388 0
None
Name [1] 299388 0
Address [1] 299388 0
Country [1] 299388 0
Other collaborator category [1] 280218 0
Other Collaborative groups
Name [1] 280218 0
Australian national nuclear research and development organisation (ANSTO, Australia).
Address [1] 280218 0
New Illawarra Rd
Lucas Heights
NSW 2234
Country [1] 280218 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300857 0
St Vincent's Hospital HREC
Ethics committee address [1] 300857 0
St Vincent's Hospital Research Office
Translational Research Centre
97-105 Boundary St
Darlinghurst NSW 2010
Ethics committee country [1] 300857 0
Australia
Date submitted for ethics approval [1] 300857 0
28/08/2015
Approval date [1] 300857 0
11/11/2015
Ethics approval number [1] 300857 0
HREC/15/SVH/320

Summary
Brief summary
The aim of this study is to test the safety and effectiveness of prostate specific membrane antigen (PSMA) labelled with a radioactive substance called Lutetium-177 (177Lu) in progressive prostate cancer patients.

Who is it for?
You may be eligible to join this study if you are aged 18 years or over and have a progressive PSMA expressing castration-resistant prostate cancer.

Study details
Participants will receive up to four 42-day cycles, with each cycle requiring a single intravenous injection of a radioactive substance called therapeutic 177 Lu-PSMA.

The exact number of treatment cycles administered and dose given will be determined by the treating doctor. Participants will then be followed for one year after completion of study to assess safety and effectiveness of the intervention.

Study rationale
Using PSMA labelled molecules enables targeted delivery of high doses radiation to sites of prostate cancer. This treatment is called radionuclide therapy and it aims to minimise radiation of most normal tissue sites.

Study Declarations
This is a new type of treatment and long-term response and toxicity data are not yet available. The drugs used in this study are not approved by the Therapeutic Goods Administration (TGA) and considered an experimental treatment.

This research has been initiated by the study doctor, A/Prof Louise Emmett, and is sponsored by St Vincent’s Hospital Sydney with funding provided by the St Vincent’s Prostate Cancer Centre. This will allow you to have the LuPSMA treatment free of charge for your conduct of the research.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85054 0
A/Prof Louise Emmett
Address 85054 0
St Vincent's Hospital
Dept. Nuclear Medicine & PET
390 Victoria Street
Darlinghurst
NSW 2010
Country 85054 0
Australia
Phone 85054 0
+61 2 8382 2216
Fax 85054 0
Email 85054 0
Louise.Emmett@svha.org.au
Contact person for public queries
Name 85055 0
Mr Robert Kent
Address 85055 0
The Kinghorn Cancer Centre
370 Victoria St
Darlinghurst
NSW 2010
Country 85055 0
Australia
Phone 85055 0
+61 2 9355 5655
Fax 85055 0
Email 85055 0
SVHS.CancerResearch@svha.org.au
Contact person for scientific queries
Name 85056 0
Mr Robert Kent
Address 85056 0
The Kinghorn Cancer Centre
370 Victoria St
Darlinghurst
NSW 2010
Country 85056 0
Australia
Phone 85056 0
+61 2 9355 5655
Fax 85056 0
Email 85056 0
SVHS.CancerResearch@svha.org.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