COVID-19 studies are our top priority. For all other trials, there is a 4-week delay in processing a trial submitted/resubmitted to the ANZCTR and additional delays for updates of registered trials. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04343885




Registration number
NCT04343885
Ethics application status
Date submitted
1/04/2020
Date registered
13/04/2020
Date last updated
23/11/2020

Titles & IDs
Public title
In Men With Metastatic Prostate Cancer, What is the Safety and Benefit of Lutetium-177 PSMA Radionuclide Treatment in Addition to Chemotherapy
Scientific title
UpFrontPSMA : A Randomised Phase 2 Study of Sequential 177Lu-PSMA617 and Docetaxel Versus Docetaxel in Metastatic Hormone-Naive Prostate Cancer
Secondary ID [1] 0 0
19/195
Universal Trial Number (UTN)
Trial acronym
UpFrontPSMA
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 177Lu-PSMA-617
Treatment: Drugs - Docetaxel

Experimental: 177Lu-PSMA+ Docetaxel - 7.5 GBq (± 10%) 177Lu-PSMA every 6 weeks x 2 cycles. Docetaxel 75 mg/m2 commencing 6 weeks later, every 3 weeks x 6 cycles

Other: Docetaxel (Control) - Docetaxel 75 mg/m2 every 3 weeks x 6 cycles


Treatment: Drugs: 177Lu-PSMA-617
Patients will be given 7.5GBq of 177Lu-PSMA every 6 weeks for 2 cycles.

Treatment: Drugs: Docetaxel
Docetaxel 75 mg/m2 given every 3 weeks for 6 cycles

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Undetectable prostate specific antigen (PSA) rate at 12 months after commencement of protocol therapy - Undetectable PSA is defined as PSA = 0.2ng/ml at 12 months after protocol treatment commencement. Patients who experience unequivocal radiographic (by conventional imaging modality) and/or clinical disease progression within 12 months of initiating protocol treatment will be considered as not having undetectable PSA at 12 months.
Timepoint [1] 0 0
Upto 32 months assuming 18 months to complete recruitment, a maximum of 1.6 months from consent to commencement of treatment for last patient and then 12 months from commencement of treatment for last patient.
Secondary outcome [1] 0 0
Safety of 177Lu-PSMA followed by docetaxel compared to docetaxel alone - The type, grade and relationship to treatment of adverse events (AE) will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
Timepoint [1] 0 0
Through completion of treatment, maximum 26 months.
Secondary outcome [2] 0 0
Time to development of castration resistance between treatment Arms - Castration resistance is defined as rising PSA and/or radiographic progression despite castrate levels of testosterone (= 50ng/dL or = 1.73nmol/L).To be measured from the date of randomisation to the date of first evidence of castration resistance.
Timepoint [2] 0 0
Through study completion, up until 2 years after the last patient commences treatment.
Secondary outcome [3] 0 0
PSA-progression free survival (PSA-PFS) between treatment Arms - PSA progression is defined as a rise in PSA by more than 25% AND more than 2ng/mL above the nadir (lowest PSA point). This needs to be confirmed by a repeat PSA performed at least 3 weeks later. Early rises in PSA prior to 12 weeks will be disregarded in determining PSA progression. To be measured from the date of randomisation to the first date of evidence of PSA progression or date of death due to any cause.
Timepoint [3] 0 0
Through study completion, up until 2 years after the last patient commences treatment.
Secondary outcome [4] 0 0
Radiographic-PFS (rPFS) between treatment Arms - Radiographic progression will be assessed by the investigator per RECIST1.1 for soft tissue and PCWG3 for bone lesions. To be measured from randomisation to the first date of documented radiographic progression using conventional imaging or death due to any cause, whichever occurs first.
Timepoint [4] 0 0
Through study completion, up until 2 years after the last patient commences treatment.
Secondary outcome [5] 0 0
Early PSMA PET response between treatment Arms - PSMA PET response assessed 3 months after treatment commencement defined by central imaging review of 68Ga-PSMA PET CT images.
Timepoint [5] 0 0
Through completion of 3 months after treatment commencement for last patient, maximum 23 months.
Secondary outcome [6] 0 0
Describe and compare health-related QoL within 12 months of treatment commencement between treatment Arms - QoL will be assessed using the Functional Assessment of Cancer Therapy for Prostate Cancer (FACT-P) questionnaire. The primary endpoint for QoL is the area under the curve (AUC) of the trial outcome index (TOI).
QoL will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months and will be scored according to the respective manuals.
Timepoint [6] 0 0
Through completion of 12 months after treatment commencement of last patient, maximum 32 months.
Secondary outcome [7] 0 0
Describe and compare pain within 12 months of treatment commencement between treatment Arms - Pain will be assessed using the Brief Pain Inventory - Short Form (BPI-SF). The primary endpoint for pain is the area under the curve (AUC) of the worst pain in 24h.
Pain and QoL will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months and will be scored according to the respective manuals.
Timepoint [7] 0 0
Through completion of 12 months after treatment commencement of last patient, maximum 32 months.
Secondary outcome [8] 0 0
Overall survival (OS) between treatment Arms - OS is defined as the time from randomisation to the date of death due to any cause.
Timepoint [8] 0 0
Through study completion, up until 2 years after the last patient commences treatment.

Eligibility
Key inclusion criteria
Inclusion Criteria for study registration:

1. Patient has provided written informed consent

2. Male aged 18 years or older at screening

3. Prostate cancer diagnosed within 12 weeks of commencement of screening

4. Histologically or cytologically confirmed adenocarcinoma of the prostate without
significant neuroendocrine differentiation or small cell histology OR metastatic
disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or
para-aortic lymph nodes) with a rising serum PSA

5. Evidence of metastatic disease on CT and/or bone scan

6. PSA > 10ng/ml prior to commencement of medical ADT or surgical orchidectomy

7. Adequate haematological, renal and hepatic functions as defined by:

- Absolute neutrophil count >1.5 x 109/L

- Platelet count >100 x 109/L

- Haemoglobin = 90g/L (no red blood cell transfusion in 4 weeks prior to
randomisation)

- Creatinine Clearance = 40mL/min (Cockcroft-Gault formula)

- Total bilirubin < 1.5 x ULN (or if bilirubin is between 1.5-2x ULN, must have a
normal conjugated bilirubin)

- Aspartate transaminase (AST) or alanine transaminase (ALT) = 2.0 x ULN (or = 5.0
x ULN in the presence of liver metastases)

8. Have a performance status of 0-2 on the ECOG Performance Scale (see Appendix 1)

9. Life expectancy greater than 6 months with treatment

10. Assessed by a medical oncologist as suitable for treatment with docetaxel

11. Patients must agree to use an adequate method of contraception

12. Willing and able to comply with all study requirements, including all treatments and
required assessments including follow-up
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria for Registration:

1. Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate
cancer. The following exceptions are permitted:

- Up to 4 weeks of ADT with luteinising hormone releasing hormone agonists or
antagonists or orchiectomy ± concurrent anti-androgens are permitted prior to
commencement of screening. At investigator discretion, patients may start ADT at
commencement of protocol therapy

- Up to one course of palliative radiation or surgical therapy to treat symptoms
resulting from metastatic disease if it was administered at least 28 days prior
to registration

2. Symptomatic cord compression, or clinical or imaging findings concerning for impending
cord compression

3. Central nervous system metastases

4. Superscan, defined as diffuse, intense, skeletal uptake on bone scan with absent renal
and background activity

5. Patients with Sjogren's syndrome

6. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the patient's
participation for the full duration of the trial, or is not in the best interest of
the patient to participate, in the opinion of the treating investigator

7. Prior diagnosis of another cancer that was:

- More than 3 years prior to current diagnosis with subsequent evidence of disease
recurrence or clinical expectation of recurrence greater than 10%

- Within 3 years of current diagnosis with the exception of successfully treated
basal cell or squamous cell skin carcinoma or adequately treated non-muscle
invasive bladder cancer (Tis, Ta and low grade T1 tumours)

Inclusion Criteria for Randomisation:

1. Significant PSMA avidity on 68Ga-PSMA PET/CT, defined after central review as a
minimum uptake of SUVmax 15 at a site of disease, and SUVmax > 10 at sites of
measurable disease =15mm (unless subject to factors explaining a lower uptake, e.g.
respiratory motion, reconstruction artefact)

2. High-volume metastatic disease on 68Ga-PSMA PET/CT defined as visceral metastases or =
4 bone metastases with = 1 outside the vertebral column and pelvis (extra-axial
skeleton)

3. Patient continues to meet all the inclusion criteria for registration

Exclusion Criteria for Randomisation:

1. Major FDG-PET discordance defined as presence of FDG positive disease with minimal PSMA
expression in multiple sites (>5) or in more than 50% of total disease volume 2. All the
exclusion criteria for registration continue to not apply

-

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
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)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Sydney
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Austin Health - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
4029 - Brisbane
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
3084 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Movember Foundation
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Prostate Cancer Research Alliance
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
United States Department of Defense
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Commercial sector/Industry
Name [4] 0 0
Advanced Accelerator Applications
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Australian Nuclear Science and Technology Organisation (ANSTO)
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Australasian Radiopharmaceutical Trials network (ARTnet)
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
Centre for Biostatistics and Clinical Trials (BaCT)
Address [8] 0 0
Country [8] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This phase 2 randomised clinical trial will compare the effectiveness of Lu-PSMA therapy
followed by docetaxel chemotherapy versus docetaxel chemotherapy on its own in patients with
newly-diagnosed high-volume metastatic hormone-naive prostate cancer (mHNPC).
Trial website
https://clinicaltrials.gov/show/NCT04343885
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Arun Azad, MBBS PhD FRACP
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Arun Azad, MBBS PhD FRACP
Address 0 0
Country 0 0
Phone 0 0
+613 855 97165
Fax 0 0
Email 0 0
Arun.Azad@petermac.org
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04343885