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Trial registered on ANZCTR


Registration number
ACTRN12617001590358
Ethics application status
Approved
Date submitted
22/11/2017
Date registered
29/11/2017
Date last updated
14/01/2021
Date data sharing statement initially provided
18/09/2019
Date results provided
14/01/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
TheraP: A randomised phase 2 trial of 177-Lutetium-Prostate Specific Membrane Antigen-617 (177Lu-PSMA617) theranostic versus cabazitaxel in progressive metastatic castration resistant prostate cancer (ANZUP1603)
Scientific title
TheraP: A randomised phase 2 trial of 177Lu-PSMA617 theranostic versus cabazitaxel in progressive metastatic castration resistant prostate cancer (ANZUP1603)
Secondary ID [1] 293348 0
Nil known
Universal Trial Number (UTN)
Trial acronym
TheraP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer 305455 0
Condition category
Condition code
Cancer 304724 304724 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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 (as determined by physician review of SPECT/CT scans), treatment will be paused, but can be recommenced up to the maximum of 6 cycles upon progression.

Adherence will be monitored by attendance at scheduled hospital treatment visits.
Intervention code [1] 299601 0
Treatment: Other
Intervention code [2] 299602 0
Treatment: Drugs
Comparator / control treatment
Patients randomised to the Cabazitaxel arm will receive 20mg/m^2 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.

Adherence will be monitored by attendance at scheduled hospital treatment visits.
Control group
Active

Outcomes
Primary outcome [1] 303932 0
Prostate Specific Antigen (PSA) response rate, defined as a reduction of >=50% from baseline (assessed from blood samples).
Timepoint [1] 303932 0
PSA assessed at baseline, every 3 weeks whilst on study treatment, once at 30-42 days after the last dose of study treatment and every 4 weeks until radiological progression.
Secondary outcome [1] 340485 0
Pain response rate, defined as:
- >=2 point reduction in PPI score from baseline with no increase in analgesic score; and/or
- >=50% decrease in analgesic score with no increase in PPI

PPI: McGill-Melzack Present Pain Intensity Scale (PPI)
Analgesic score: Using Morphine Equivalent Daily Dose (MEDD)
Timepoint [1] 340485 0
Assessed every 3 weeks whilst on study treatment, once at 30-42 days after the last dose of study treatment and every 4 weeks until radiological progression.
Secondary outcome [2] 340486 0
Objective Tumour Response Rate - defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) divided by the total number of participants (using RECIST 1.1).
Timepoint [2] 340486 0
SPECT/CT (177Lu-PSMA617 arm only) - at 24 hours after every 177Lu-PSMA617 administration;
CT CAP and Radioisotope bone scan - at baseline, weeks 11, 23 and 35 and then every 12 weeks until radiological progression.
Secondary outcome [3] 340487 0
Progression free survival - the time from randomisation to date of PSA progression (blood samples), pain progression (on PPI) or radiographic progression (PCWG3 for bone and RECIST 1.1 for soft tissue), whichever occurs first.
Timepoint [3] 340487 0
PSA blood samples and PPI at baseline, every 3 weeks whilst on study treatment, once at 30-42 days after the last dose of study treatment and every 4 weeks until radiological progression.
SPECT/CT (177Lu-PSMA617 arm only) - at 24 hours after every 177Lu-PSMA617 administration;
CT CAP and Radioisotope bone scan - at baseline, weeks 11, 23 and 35 and then every 12 weeks until radiological progression.
Secondary outcome [4] 340488 0
PSA progression free survival, defined as the time from randomisation to PSA progression, assessed using PCWG3 criteria on blood test results.
Timepoint [4] 340488 0
PSA blood samples at baseline, every 3 weeks whilst on study treatment, once at 30-42 days after the last dose of study treatment and every 4 weeks until radiological progression.
Secondary outcome [5] 340489 0
Pain progression free survival - defined as the time from randomisation to pain progression (>=1 point increase on PPI from nadir and >=25% increase in analgesic score (MEDD) from nadir, OR need for palliative radiotherapy).
Timepoint [5] 340489 0
Assessed at baseline, every 3 weeks whilst on study treatment, once at 30-42 days after the last dose of study treatment and every 4 weeks until radiological progression.
Secondary outcome [6] 340490 0
Radiographic progression free survival - defined as the time from randomisation to radiographic progression (assessed using PCWG3 criteria for bone lesions and RECIST 1.1 for soft tissue lesions).
Timepoint [6] 340490 0
SPECT/CT (177Lu-PSMA617 arm only) - at 24 hours after every 177Lu-PSMA617 administration;
CT CAP and Radioisotope bone scan - at baseline, weeks 11, 23 and 35 and then every 12 weeks until radiological progression.
Secondary outcome [7] 340491 0
Aspects of health-related quality of life, assessed using the EORTC core quality of life questionnaire (QLQ C-30) and the Patient Disease and Treatment Assessment Form (PDF).
Timepoint [7] 340491 0
Every 3 weeks whilst on study treatment, once at 30-42 days after the last dose of study treatment and every 4 weeks until radiological progression.
Secondary outcome [8] 340492 0
Overall survival - time from registration to death from any cause or last known follow-up alive.
Timepoint [8] 340492 0
Assessed at all study visits (3-weekly whilst on treatment then 4-weekly until radiological progression, then every 12 weeks following radiological progression).
Secondary outcome [9] 340493 0
Frequency and severity of adverse events (composite), assessed using CTCAE v4.03.
Timepoint [9] 340493 0
Assessed 3-weekly whilst on treatment, once at 30-42 days after last dose, then 4-weekly until 12 weeks after last dose.
Secondary outcome [10] 340907 0
Exploratory tertiary objective: Associations between 68Ga-PSMA PET/CT, FDG PET/CT, baseline characteristics, and outcomes
Timepoint [10] 340907 0
End of data collection
Secondary outcome [11] 340908 0
Exploratory tertiary objective: Associations between clinical outcomes and possible prognostic and/or predictive biomarkers (tissue and circulating) including ctDNA
Timepoint [11] 340908 0
End of data collection

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 >= 20ng/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 x10^9/L
• Hb >=90g/L (no red blood cell transfusion in last 4 weeks)
• Neutrophils > 1.5 x10^9/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)
Central randomisation by Flexetrials computer software
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Minimisation approach using Flexetrials randomisation software, with stratification for study site, volume of disease (>20 versus <=20 sites of disease measured on 68Ga-PSMA PET/CT), and prior treatment with abiraterone or enzalutamide (Yes/No).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A trial of 200 participants randomised in 1:1 ratio to Lu-PSMA or cabazitaxel would have 80% power at the two-sided 5% level of significance to reject the null hypothesis of no difference between groups in PSA response rates if the true rates were actually 40% for cabazitaxel versus 60% for Lu-PSMA. The sample size incorporates an allowance of 3% for ineligible and/or inevaluable participants.
The study has 80% power at the two-sided 5% level of significance to reject the null hypothesis of no treatment effect on PFS if the true hazard ratio (HR) was 0.65, and assuming a median progression progression-free survival of 3 months in those allocated cabazitaxel, 24 months for accrual, and an additional 6 months for follow-up.
The study has 80% power at the two-sided 5% level of significance to reject the null hypothesis of no treatment effect on OS after 170 deaths have occurred if the true HR was 0.65. This number of deaths would be expected with 40 months of follow-up beyond the 24 months accrual period, assuming a median OS of 15 months in those allocated cabazitaxel and a true HR for OS of 0.65.
The estimates of PSA response, median PFS, and median OS for cabazitaxel are informed by the results of the TROPIC study. The hypothesised magnitude of the additional benefit to these endpoints with Lu-PSMA are judged to be clinically plausible and worthwhile.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
31/01/2018
Actual
8/02/2018
Date of last participant enrolment
Anticipated
30/11/2019
Actual
10/09/2019
Date of last data collection
Anticipated
30/04/2021
Actual
Sample size
Target
200
Accrual to date
Final
201
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 9384 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 9386 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 9387 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 9388 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [5] 9390 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [6] 9391 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 9392 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [8] 9393 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [9] 9727 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [10] 11797 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [11] 11798 0
Monash Medical Centre - Moorabbin campus - East Bentleigh
Recruitment postcode(s) [1] 18078 0
2065 - St Leonards
Recruitment postcode(s) [2] 18080 0
2170 - Liverpool
Recruitment postcode(s) [3] 18081 0
3000 - Melbourne
Recruitment postcode(s) [4] 18082 0
3084 - Heidelberg
Recruitment postcode(s) [5] 18084 0
4029 - Herston
Recruitment postcode(s) [6] 18085 0
5000 - Adelaide
Recruitment postcode(s) [7] 18086 0
6009 - Nedlands
Recruitment postcode(s) [8] 18087 0
6150 - Murdoch
Recruitment postcode(s) [9] 18504 0
2010 - Darlinghurst
Recruitment postcode(s) [10] 23923 0
2298 - Waratah
Recruitment postcode(s) [11] 23924 0
3165 - East Bentleigh

Funding & Sponsors
Funding source category [1] 297970 0
Charities/Societies/Foundations
Name [1] 297970 0
Prostate Cancer Foundation Australia
Country [1] 297970 0
Australia
Funding source category [2] 297974 0
Commercial sector/Industry
Name [2] 297974 0
Endocyte
Country [2] 297974 0
United States of America
Funding source category [3] 297975 0
Government body
Name [3] 297975 0
Australian Nuclear Science and Technology Organisation (ANSTO)
Country [3] 297975 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Address
Lifehouse, Level 6, 119-143 Missenden Road, Camperdown, NSW 2050
Country
Australia
Secondary sponsor category [1] 297038 0
None
Name [1] 297038 0
None
Address [1] 297038 0
None
Country [1] 297038 0
Other collaborator category [1] 279799 0
Other
Name [1] 279799 0
NHMRC Clinical Trials Centre
Address [1] 279799 0
Lifehouse, Level 6, 119-143 Missenden Road, Camperdown, NSW 2050
Country [1] 279799 0
Australia
Other collaborator category [2] 279800 0
Other Collaborative groups
Name [2] 279800 0
Australasian Radiopharmaceutical Trials network (ARTnet)
Address [2] 279800 0
PO Box 2195, Wellington Point QLD 4160
Country [2] 279800 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299010 0
Peter MacCallum HREC
Ethics committee address [1] 299010 0
Ethics committee country [1] 299010 0
Australia
Date submitted for ethics approval [1] 299010 0
10/07/2017
Approval date [1] 299010 0
01/11/2017
Ethics approval number [1] 299010 0
17/109

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

Contacts
Principal investigator
Name 78990 0
A/Prof Michael Hofman
Address 78990 0
Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne VIC 3000
Country 78990 0
Australia
Phone 78990 0
+61 2 9562 5000
Fax 78990 0
Email 78990 0
[email protected]
Contact person for public queries
Name 78991 0
Ailsa Langford
Address 78991 0
NHMRC CTC, level 6, Lifehouse, 119-143 Missenden Rd, Camperdown, NSW 2050
Country 78991 0
Australia
Phone 78991 0
+61 2 9562 5000
Fax 78991 0
Email 78991 0
[email protected]
Contact person for scientific queries
Name 78992 0
Ailsa Langford
Address 78992 0
NHMRC CTC, level 6, Lifehouse, 119-143 Missenden Rd, Camperdown, NSW 2050
Country 78992 0
Australia
Phone 78992 0
+61 2 9562 5000
Fax 78992 0
Email 78992 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Please contact NHMRC CTC for data sharing policy.


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.