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Trial registered on ANZCTR


Registration number
ACTRN12618001073291
Ethics application status
Approved
Date submitted
1/12/2017
Date registered
27/06/2018
Date last updated
11/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
An early phase clinical trial evaluating the effectiveness of treatment of 177Lu-PSMA with idronoxil in men with castrate-resistant prostate cancer (LuPin Trial)
Scientific title
Radionuclide therapy using 177Lu-PSMA: extension of a pilot study in men with castrate-resistant prostate cancer to determine the clinical benefit of combination therapy with idronoxil
Secondary ID [1] 293512 0
Nil Known
Universal Trial Number (UTN)
U1111-1206-1132
Trial acronym
LuPin
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Castrate-resistant prostate cancer 305696 0
Condition category
Condition code
Cancer 304916 304916 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This an open label non-randomised phase I study in men with prostate specific membrane antigen (PSMA) positive, hormone refractory, progressive prostate cancer present within the preceding 6 months based on radiology and or symptomatic progression.

There are two cohorts which will receive up to six cycles of therapeutic 177 Lu-PSMA combined with either idronoxil 400 mg daily or idronoxil 800 mg daily depending on patient response. Each cohort will undergo a 42 day treatment cycle with a single IV injection of 177 Lu-PSMA on day 0 of each cycle. The dose given is calculated by the doctor based on the participant's weight and volume of disease. Dose will vary between individuals. Both cohorts, following administration of 177 Lu-PSMA, will provided with the appropriate idronoxil to self administer at home once a day for the following 9 days. Idronoxil are suppositories and participants will be instructed on the method of administration and provided with instruction sheet.

Participants will routinely follow up with treating doctor before each cycle to assess benefit of treatment and adherence to study. Each 42 day cycle will follow the same plan and the participant will continue onto next cycle with .
Intervention code [1] 299744 0
Treatment: Drugs
Intervention code [2] 299875 0
Treatment: Other
Comparator / control treatment
The 400 mg daily cohort will be compared to the 800 mg daily cohort.
Control group
Dose comparison

Outcomes
Primary outcome [1] 304109 0
To determine the toxicity profile of combination therapy of idronoxil and 177Lu PSMA graded by CTCAE version 4.03
Timepoint [1] 304109 0
The assessments will occur at baseline, after one cycle of treatment and at the end of each cycle thereafter.
Primary outcome [2] 304257 0
To document the anti-cancer efficacy using 177Lu-PSMA-idronoxil combination therapy using a composite of surrogate measures including serum PSA, medical imaging, EORTC QLQ-C30 and BPI-SF.
Timepoint [2] 304257 0
The assessments will occur at baseline, after one cycle of treatment and at the end of each cycle thereafter.

The efficacy will be determined by
a. QOL scores (EORTC QLQ-C30)
b. Pain scores (BPI-SF)
c. Radiologic response 3 months post completion of therapy (RECIST v1.1): complete response, partial response, stable disease, progressive disease
d. 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.
e. Serum PSA response 3 months post completion of therapy.
Secondary outcome [1] 341008 0
To investigate the normal tissue bio-distribution of repeated doses of 177Lu PSMA-idronoxil combination therapy using medical imaging tools (Isotope bone scan, Contrast enhanced CT, PSMA PET/CT, FDP PET/CT and 177Lu PSMA Q-SPECT imaging).
Timepoint [1] 341008 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] 341376 0
To document the progression-free rates following combination therapy.
Timepoint [2] 341376 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] 341377 0
To document changes in serum PSMA during therapy
Timepoint [3] 341377 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).
Secondary outcome [4] 341378 0
An exploratory outcome to potentially identify biomarkers that are prognostic and/or predictive of response to treatment, safety and resistance to study treatment using serum assays.

Timepoint [4] 341378 0
Serum biomarkers of idronoxil function and response rate will be compared at baseline and post-treatment
Secondary outcome [5] 348055 0
To document the overall survival following combination therapy.
Timepoint [5] 348055 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 [6] 348056 0
To investigate the tumour localisation following repeated doses of 177Lu PSMA-idronoxil combination therapy using medical imaging tools (Isotope bone scan, Contrast enhanced CT, PSMA PET/CT, FDP PET/CT and 177Lu PSMA Q-SPECT imaging).
Timepoint [6] 348056 0
The assessments will occur at baseline, after one cycle of treatment and at the end of each cycle thereafter.
Secondary outcome [7] 348057 0
To investigate radiation dosimetry of repeated doses of 177Lu PSMA-idronoxil combination therapy using medical imaging tools (Isotope bone scan, Contrast enhanced CT, PSMA PET/CT, FDP PET/CT and 177Lu PSMA Q-SPECT imaging).
Timepoint [7] 348057 0
The assessments will occur at baseline, after one cycle of treatment and at the end of each cycle thereafter. Tumour dosimetry expressed in Gy.

Eligibility
Key inclusion criteria
1. Pathologically confirmed prostate adenocarcinoma
2. Castration-resistant metastatic disease, including prior treatment with Abiraterone, Enzalutamide or both (unless contraindicated, medically unsuitable or patient refuses)
3. Prior Taxane-based chemotherapy (unless contraindicated, medically unsuitable or patient refuses)
4. Objective evidence of disease progression within 6 months of study entry as defined by either:
a. Radiologic progression (RECIST v1.1 criteria) on conventional imaging
b. Symptoms refractory to standard medical care
5. PSMA PET/CT demonstrating uptake intensity significantly greater than liver at sites of disease
6. Written informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Estimated GFR < 40 ml/min
2. Platelet count <100, 000 x109 /L
3. Neutrophil count < 1.5 x109 /L
4. Hb < 10.0 g/dL
5. Albumin less than or equal to 25
6. Hydronephrosis (untreated)
7. Concomitant nephrotoxic drugs (e.g. aminoglycosides)
8. ECOG performance status > 3
9. Life expectancy of less than 12 weeks
10. Age <18 years
11. FDG PET/CT demonstrating sites of major discordant disease (i.e. FDG + PSMA-)
12. Recent radiotherapy (within 6 weeks) to sole sites of assessable disease
13. Uncontrolled intercurrent illness that would limit compliance with study protocols
14. Unable to comply with study protocol.

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
Parallel
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)24
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
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
Recruitment hospital [1] 9476 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 18209 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 298129 0
Commercial sector/Industry
Name [1] 298129 0
Noxopharm Limited
Address [1] 298129 0
Suite 3, Level 4 828 Pacific Hwy
Gordon NSW 2072
Country [1] 298129 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Sydney
Address
360 Victoria St
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 297209 0
None
Name [1] 297209 0
Address [1] 297209 0
Country [1] 297209 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299148 0
St Vincent's Hospital HREC
Ethics committee address [1] 299148 0
St Vincent's Hospital Research Office
Translational Research Centre
97-105 Boundary St
Darlinghurst NSW 2010
Ethics committee country [1] 299148 0
Australia
Date submitted for ethics approval [1] 299148 0
30/01/2017
Approval date [1] 299148 0
13/10/2017
Ethics approval number [1] 299148 0
HREC/17/SVH/19

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 PSMA positive, hormone refractory and progressive prostate cancer.

Study details
Participants will receive up to six 42-day cycles, with each cycle requiring a single intravenous injection of a radioactive substance called therapeutic 177 Lu-PSMA combined with NOX66. NOX66 is used to make cancer cells more sensitive to radiation treatment and is continued to be given the following 9 days after injection.

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 and Noxopharm Ltd. This will allow you to have the LuPSMA / NOX66 treatment free of charge and for the conduct of the research.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79458 0
A/Prof Louise Emmett
Address 79458 0
St Vincent’s Hospital Sydney
Nuclear Medicine and PET department
360 Victoria Street
Darlinghurst NSW 2010
Country 79458 0
Australia
Phone 79458 0
+612 8382 1824
Fax 79458 0
Email 79458 0
l.emmett@unsw.edu.au
Contact person for public queries
Name 79459 0
A/Prof Louise Emmett
Address 79459 0
St Vincent’s Hospital Sydney
Nuclear Medicine and PET department
360 Victoria Street
Darlinghurst NSW 2010
Country 79459 0
Australia
Phone 79459 0
+612 8382 1824
Fax 79459 0
Email 79459 0
l.emmett@unsw.edu.au
Contact person for scientific queries
Name 79460 0
A/Prof Louise Emmett
Address 79460 0
St Vincent’s Hospital Sydney
Nuclear Medicine and PET department
360 Victoria Street
Darlinghurst NSW 2010
Country 79460 0
Australia
Phone 79460 0
+612 8382 1824
Fax 79460 0
Email 79460 0
l.emmett@unsw.edu.au

No information has been provided regarding IPD availability
Summary results
No Results