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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05150236




Registration number
NCT05150236
Ethics application status
Date submitted
30/09/2021
Date registered
9/12/2021

Titles & IDs
Public title
EVOLUTION: 177Lu-PSMA Therapy Versus 177Lu-PSMA in Combination With Ipilimumab and Nivolumab for Men With mCRPC
Scientific title
Phase II Study of Radionuclide 177Lu-PSMA Therapy Versus 177Lu-PSMA in Combination With Ipilimumab and Nivolumab for Men With MetastaticCastration Resistant Prostate Cancer (mCRPC)
Secondary ID [1] 0 0
ANZUP 2001
Universal Trial Number (UTN)
Trial acronym
ANZUP2001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms 0 0
Genital Neoplasms, Male 0 0
Urogenital Neoplasms 0 0
Prostate Cancer 0 0
Neoplasms by Site 0 0
Neoplasms 0 0
Prostatic Disease 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate
Cancer 0 0 0 0
Any cancer
Cancer 0 0 0 0
Other cancer types
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Cancer 0 0 0 0
Penile (penis)
Cancer 0 0 0 0
Testicular

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

Experimental: Combination 177Lu-PSMA-617, Ipilimumab & Nivolumab - 177Lu-PSMA (7.5GBq) given every 6 weeks up to 6 cycles in combination with concurrent ipilimumab (3mg/kg Q6W x 4 doses) and nivolumab (1mg/kg Q3W x 8 doses) followed by nivolumab monotherapy (480mg Q4W up to 18 doses) or until disease progression or unacceptable toxicity.

Experimental: 177Lu-PSMA-617 - 177Lu-PSMA (7.5GBq) given every 6 weeks up to 6 cycles or until disease progression or unacceptable toxicity.


Treatment: Drugs: 177Lu-PSMA-617
Patients will be given 7.5GBq of Lu-PSMA every 6 weeks up to 6 cycles unless there is unacceptable toxicity, commencing following result of 68Ga-PSMA PET within 28 days of registration.

Treatment: Drugs: Ipilimumab
Patients will be given 3mg/kg of Ipilimumab every 6 weeks up to 4 doses unless there is unacceptable toxicity, concurrently with Lu-PSMA and Nivolumab.

Treatment: Drugs: Nivolumab
Patients will be given 1mg/kg of Nivolumab every 3 weeks up to 8 doses, concurrently with Lu-PSMA and Ipilimumab unless there is unacceptable toxicity. Followed by 480mg nivolumab monotherapy commencing at week 32. Nivolumab monotherapy will be given to patients every 4 weeks up to 18 doses, or until disease progression or unacceptable toxicity.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
PSA progression free survival (PSA-PFS) at 1 year (PCWG3)
Timepoint [1] 0 0
Date of randomisation to the date of first evidence of PSA progression at 53 weeks post randomisation.
Secondary outcome [1] 0 0
PSA response rate (PSA-RR)
Timepoint [1] 0 0
Date of randomisation through to study completion, approximately 3 years from start of recruitment. Early rises in PSA prior to 12 weeks will be disregarded in determining PSA response.
Secondary outcome [2] 0 0
Frequency and severity of adverse events (CTCAE v5.0)
Timepoint [2] 0 0
Date of first dose of study treatment until 100 days after cessation of study treatment.
Secondary outcome [3] 0 0
Radiological progression free survival (PCWG3/RECIST1.1)
Timepoint [3] 0 0
Date of randomisation to the date of first evidence of progression on imaging (PCWG3 criteria for bone lesions and RECIST 1.1 for soft tissue lesions) assessed every 12 weeks through to study completion, approximately 3 years from start of recruitment.
Secondary outcome [4] 0 0
PSA progression free survival (PCWG3)
Timepoint [4] 0 0
Date of randomisation through to study completion, approximately 3 years from start of recruitment.
Secondary outcome [5] 0 0
Overall survival (OS)
Timepoint [5] 0 0
Through to study completion, approximately 3 years from start of recruitment.
Secondary outcome [6] 0 0
Objective response rate (ORR)
Timepoint [6] 0 0
Date of randomisation through to study completion, approximately 3 years from start of recruitment.
Secondary outcome [7] 0 0
Duration of response
Timepoint [7] 0 0
Date of randomisation through to first radiological progression or through to study completion, approximately 3 years from start of recruitment.
Secondary outcome [8] 0 0
Time to treatment response
Timepoint [8] 0 0
Date of randomisation through to study completion, approximately 3 years from start of recruitment.
Secondary outcome [9] 0 0
Aspects of Health Related Quality of Life (HRQoL) - 1
Timepoint [9] 0 0
Within 7 days prior to randomisation, assessed every 12 weeks, through to study completion, approximately 3 years from start of recruitment.
Secondary outcome [10] 0 0
Aspects of Health Related Quality of Life (HRQoL) - 2
Timepoint [10] 0 0
Within 7 days prior to randomisation, assessed every 12 weeks, through to study completion, approximately 3 years from start of recruitment.

Eligibility
Key inclusion criteria
1. Aged 18 years or older, with histologically confirmed adenocarcinoma of the prostate.
2. Castration-resistant metastatic prostate cancer (defined as disease progressing despite castration by orchidectomy or ongoing luteinising hormone-releasing hormone agonist or antagonist).
3. Patients must have progressed on prior novel AR targeted agents for treatment of prostate cancer. Progressive disease defined by at least one of the following:

* PSA progression, minimum of two rising PSA values from a baseline measurement with an interval of = 1 week between each measurement. The PSA value at screening should be = 5ng/ml
* Soft tissue or visceral disease progression as per RECIST 1.1
* Bone progression: = 2 new lesions on bone scan as per PCWG3
4. Target or non-target lesions according to RECIST 1.1 and PCWG3
5. Significant PSMA avidity on PET/CT using 68GaPSMA, defined as SUVmax =15 at a site of disease, and SUVmax = 10 at other sites of disease =10mm (where there is no impact from partial voluming.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. Adequate bone marrow, hepatic and renal function documented within 28 days of registration, defined as:

* Haemoglobin =90 g/L independent of transfusions (no red blood cell transfusion in last 4 weeks)
* Absolute neutrophil count =1.5x109/L
* Platelets =100 x109/L
* Total bilirubin =1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome
* Aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) =2.5 × ULN or =5 × ULN for participants with liver metastases
* Serum creatinine =1.5 x ULN or a calculated creatinine clearance > 50mL/min (Cockcroft-Gault equation)
8. Patients must have a life expectancy = 24 weeks.
9. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
10. 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 known significant sarcomatoid, spindle cell or neuroendocrine cell components, or metastasis of other cancers to the prostate.
2. 18F-FDG-PET/CT SUVmax =10 at a site of measurable disease with no concurrent PSMA expression > 10mm
3. Prior treatment with anti-PD1, anti-PD-L1/L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways.
4. Patients must not have had more than one line of chemotherapy. If a patient has had docetaxel chemotherapy for hormone sensitive or castrate resistant setting, this will be considered one line.
5. Prior treatment with 177Lu-PSMA.
6. Patients with active, known, or suspected autoimmune disease. Sjogren's syndrome is considered an autoimmune disease. Exceptions: Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition only requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger, may be eligible.
7. Patients with a condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids, and adrenal replacement doses = 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
8. Participants must have recovered from all AE due to previous therapies to =Grade 1 or baseline. Participants with = Grade 2 neuropathy may be eligible.
9. Active malignancies within the previous 2-years with >30% probability of recurrence within 1 year. Melanoma in situ, basal cell or squamous cell carcinomas of skin, are permitted.
10. Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated.
11. Radiation or surgery within 2 weeks of randomisation.
12. Previous history of interstitial lung disease or non-infectious pneumonitis.
13. Administration of a live vaccine within 30 days prior to the first dose of study drug.
14. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
15. Inadequate contraception. Men must have been surgically sterilised or use a (double if required) barrier method of 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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
Accrual to date
Final
93
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
St Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [3] 0 0
Royal Brisbane and Womens hospital - Herston
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
Austin Health - Heidelberg
Recruitment hospital [6] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [7] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [8] 0 0
Sir Charles Gairdner - Nedlands
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2298 - Newcastle
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment postcode(s) [8] 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
Prostate Cancer Foundation of Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Bristol-Myers Squibb
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/industry
Name [3] 0 0
Advanced Accelerator Applications
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University of Sydney
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Shahneen Sandhu, MBBS, 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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?


Supporting document/s available: Study protocol
When will data be available (start and end dates)?
Study protocol will be published in a peer-reviewed journal within 24 months.
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05150236