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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03392428




Registration number
NCT03392428
Ethics application status
Date submitted
11/12/2017
Date registered
8/01/2018
Date last updated
13/06/2022

Titles & IDs
Public title
A Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer
Scientific title
TheraP: A Randomised Phase 2 Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer (ANZUP Protocol 1603)
Secondary ID [1] 0 0
ANZUP 1603
Universal Trial Number (UTN)
Trial acronym
TheraP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer of the Prostate 0 0
Metastatic Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - 177Lu-PSMA617
Treatment: Drugs - Cabazitaxel

Experimental: 177Lu-PSMA617 - Patients randomised to the 177Lu-PSMA617 arm will receive 6-8.5GBq of 177Lu-PSMA617 by intravenous injection once every 6 weeks until progressive disease, prohibitive toxicity or a maximum of 6 cycles.

The first dose will be administered at 8.5GBq, reducing by 0.5GBq with every cycle given (i.e. to 6.0GBq on the sixth cycle, if reached). In some patients who have an exceptional response, treatment will be paused but can be re-commenced up to the maximum of 6 cycles upon progression.

Active comparator: Cabazitaxel - Patients randomised to the Cabazitaxel arm will receive 20mg/m2 Cabazitaxel by intravenous infusion once every 3 weeks until progressive disease, prohibitive toxicity or a maximum of 10 cycles.

Patients in this arm will also receive prednisolone 10mg orally per day for the duration of their cabazitaxel treatment.


Other interventions: 177Lu-PSMA617
Patients randomised to the 177Lu-PSMA617 arm will receive 6-8.5GBq of 177Lu-PSMA617 by intravenous injection once every 6 weeks until progressive disease, prohibitive toxicity or a maximum of 6 cycles.

The first dose will be administered at 8.5GBq, reducing by 0.5GBq with every cycle given (i.e. to 6.0GBq on the sixth cycle, if reached). In some patients who have an exceptional response, treatment will be paused but can be re-commenced up to the maximum of 6 cycles upon progression.

Treatment: Drugs: Cabazitaxel
Patients randomised to the Cabazitaxel arm will receive 20mg/m2 Cabazitaxel by intravenous infusion once every 3 weeks until progressive disease, prohibitive toxicity or a maximum of 10 cycles.

Patients in this arm will also receive prednisolone 10mg orally per day for the duration of their cabazitaxel treatment.
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Prostate Specific Antigen response rate (PSA RR)
Timepoint [1] 0 0
Through study completion, on average 4 years
Secondary outcome [1] 0 0
Pain Response (PPI and Analgesic Score)
Timepoint [1] 0 0
Through study completion, on average 4 years
Secondary outcome [2] 0 0
Objective Tumour Response Rate
Timepoint [2] 0 0
Through study completion, on average 4 years
Secondary outcome [3] 0 0
Progression free survival
Timepoint [3] 0 0
Through study completion, on average 4 years
Secondary outcome [4] 0 0
PSA progression free survival
Timepoint [4] 0 0
Through study completion, on average 4 years
Secondary outcome [5] 0 0
Pain progression free survival
Timepoint [5] 0 0
Through study completion, on average 4 years
Secondary outcome [6] 0 0
Radiographic progression free survival
Timepoint [6] 0 0
Through study completion, on average 4 years
Secondary outcome [7] 0 0
Health-related quality of life
Timepoint [7] 0 0
Through study completion, on average 4 years
Secondary outcome [8] 0 0
Overall survival
Timepoint [8] 0 0
Through study completion, on average 4 years
Secondary outcome [9] 0 0
Frequency and severity of adverse events
Timepoint [9] 0 0
From first study dose to 12 weeks after completing study treatment

Eligibility
Key inclusion criteria
1. Male aged 18 or older with metastatic adenocarcinoma of the prostate defined by:

* Documented histopathology of prostate adenocarcinoma OR
* Metastatic disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes)
2. Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing Luteinizing Hormone-Releasing Hormone (LHRH) analog
3. Progressive disease with rising PSA on 3 consecutive measurements, and PSA = 20 ng/mL
4. Target or non-target lesions according to RECIST 1.1
5. Prior treatment with docetaxel
6. Significant PSMA avidity on 68Ga-PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax > 10 at sites of measurable disease =10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact)
7. ECOG Performance status 0 to 2
8. Assessed by a medical oncologist as suitable for chemotherapy with cabazitaxel
9. Adequate renal function:

• Cr Cl = 40mL/min (Cockcroft-Gault formula)
10. Adequate bone marrow function:

* Platelets = 100 x10 billion /L
* Hb = 90g/L (no red blood cell transfusion in last 4 weeks)
* Neutrophils > 1.5 x10 billion/L
11. Adequate liver function:

* Bilirubin < 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5-2x ULN, must have a normal conjugated bilirubin)
* AST or ALT = 2.0 x ULN (or = 5.0 x ULN in the presence of liver metastases)
12. Estimated life expectancy > 12 weeks
13. Study treatment both planned and able to start within 21 days of randomisation
14. Willing and able to comply with all study requirements, including all treatments (cabazitaxel or Lu-PSMA); and, the timing and nature of all required assessments
15. Signed, written informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
2. Site(s) of disease that are FDG positive with minimal PSMA expression defined as FDG intensity > 68Ga-PSMA activity OR 68Ga-PSMA SUVmax < 10
3. Sjogren's syndrome
4. Prior treatment with cabazitaxel or Lu-PSMA
5. Contraindications to the use of corticosteroid treatment
6. Active malignancy other than prostate cancer
7. Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
8. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse
9. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/01/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/12/2021
Sample size
Target
Accrual to date
Final
201
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
St Vincent's Hospital - Sydney
Recruitment hospital [3] 0 0
Royal North Shore Hospital - Sydney
Recruitment hospital [4] 0 0
Calvary Mater Newcastle Hospital - Waratah
Recruitment hospital [5] 0 0
Royal Brisbane and Womens Hospital - Brisbane
Recruitment hospital [6] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [8] 0 0
Austin Hospital - Melbourne
Recruitment hospital [9] 0 0
Monash Moorabbin Hospital - Moorabbin
Recruitment hospital [10] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [11] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
2065 - Sydney
Recruitment postcode(s) [4] 0 0
2298 - Waratah
Recruitment postcode(s) [5] 0 0
4029 - Brisbane
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
3008 - Melbourne
Recruitment postcode(s) [8] 0 0
3084 - Melbourne
Recruitment postcode(s) [9] 0 0
3165 - Moorabbin
Recruitment postcode(s) [10] 0 0
6450 - Murdoch
Recruitment postcode(s) [11] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Other
Name
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australian Nuclear Science and Technology Organisation (ANSTO)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Endocyte
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Prostate Cancer Foundation of Australia (PCFA)
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Australasian Radiopharmaceutical Trials network (ARTnet)
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Movember Foundation
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This open label, randomised, stratified, 2-arm, multicentre, phase 2 trial aims to determine the activity and safety of Lu-PSMA vs cabazitaxel in men with progressive metastatic castration resistant prostate cancer
Trial website
https://clinicaltrials.gov/study/NCT03392428
Trial related presentations / publications
Viljoen B, Hofman MS, Chambers SK, Dunn J, Dhillon HM, Davis ID, Ralph N. Experiences of participants in a clinical trial of a novel radioactive treatment for advanced prostate cancer: A nested, qualitative longitudinal study. PLoS One. 2022 Nov 9;17(11):e0276063. doi: 10.1371/journal.pone.0276063. eCollection 2022.
Buteau JP, Martin AJ, Emmett L, Iravani A, Sandhu S, Joshua AM, Francis RJ, Zhang AY, Scott AM, Lee ST, Azad AA, McJannett MM, Stockler MR, Williams SG, Davis ID, Hofman MS; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. PSMA and FDG-PET as predictive and prognostic biomarkers in patients given [177Lu]Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): a biomarker analysis from a randomised, open-label, phase 2 trial. Lancet Oncol. 2022 Nov;23(11):1389-1397. doi: 10.1016/S1470-2045(22)00605-2. Epub 2022 Oct 16.
Viljoen B, Hofman MS, Chambers SK, Dunn J, Dhillon H, Davis ID, Ralph N. Advanced prostate cancer experimental radioactive treatment-clinical trial decision making: patient experiences. BMJ Support Palliat Care. 2021 Aug 9:bmjspcare-2021-002994. doi: 10.1136/bmjspcare-2021-002994. Online ahead of print.
Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 27;397(10276):797-804. doi: 10.1016/S0140-6736(21)00237-3. Epub 2021 Feb 11.
Iravani A, Violet J, Azad A, Hofman MS. Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies. Prostate Cancer Prostatic Dis. 2020 Mar;23(1):38-52. doi: 10.1038/s41391-019-0174-x. Epub 2019 Oct 8.
Public notes

Contacts
Principal investigator
Name 0 0
Michael Hofman, A/Prof
Address 0 0
Peter MacCallum Cancer Centre, Melbourne, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03392428