Trial from ClinicalTrials.gov

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Trial ID
NCT03392428
Ethics application status
Date submitted
11/12/2017
Date registered
11/12/2017
Date last updated
5/02/2018

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) - PSA RR defined as the proportion of participants in each group with a PSA reduction of = 50% from baseline.
Timepoint [1] 0 0
Through study completion, on average 4 years
Secondary outcome [1] 0 0
Pain Response (PPI and Analgesic Score) - 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] 0 0
Through study completion, on average 4 years
Secondary outcome [2] 0 0
Objective Tumour Response Rate - 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] 0 0
Through study completion, on average 4 years
Secondary outcome [3] 0 0
Progression free survival - 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] 0 0
Through study completion, on average 4 years
Secondary outcome [4] 0 0
PSA progression free survival - PSA progression free survival, defined as the time from randomisation to PSA progression, assessed using PCWG3 criteria on blood test results.
Timepoint [4] 0 0
Through study completion, on average 4 years
Secondary outcome [5] 0 0
Pain progression free survival - 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] 0 0
Through study completion, on average 4 years
Secondary outcome [6] 0 0
Radiographic progression free survival - 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] 0 0
Through study completion, on average 4 years
Secondary outcome [7] 0 0
Health-related quality of life - Health-related quality of life, assessed using a composite of the EORTC core quality of life questionnaire (QLQ C-30) and the Patient Disease and Treatment Assessment Form (PDF).
Timepoint [7] 0 0
Through study completion, on average 4 years
Secondary outcome [8] 0 0
Overall survival - Overall survival - time from registration to death from any cause or last known follow-up alive.
Timepoint [8] 0 0
Through study completion, on average 4 years
Secondary outcome [9] 0 0
Frequency and severity of adverse events - Frequency and severity of adverse events (composite), assessed using CTCAE v4.03.
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
Gender
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
Blinded (masking 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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
QLD,VIC
Recruitment hospital [1] 0 0
Royal Brisbane and Womens Hospital - Brisbane
Recruitment hospital [2] 0 0
Peter Mac Callum - Melbourne
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 0 0
3008 - Melbourne

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

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
Trial related presentations / publications
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
Anne Woollett
Address 0 0
Country 0 0
Phone 0 0
61295625033
Fax 0 0
Email 0 0
anne.woollett@anzup.org.au
Contact person for scientific queries
Contact person responsible for updating information