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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT05150236
Registration number
NCT05150236
Ethics application status
Date submitted
30/09/2021
Date registered
9/12/2021
Date last updated
15/12/2023
Titles & IDs
Public title
EVOLUTION: 177Lu-PSMA Therapy Versus 177Lu-PSMA in Combination With Ipilimumab and Nivolumab for Men With mCRPC
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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)
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Secondary ID [1]
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ANZUP 2001
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Universal Trial Number (UTN)
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Trial acronym
ANZUP2001
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms
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Genital Neoplasms, Male
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Urogenital Neoplasms
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Prostate Cancer
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Neoplasms by Site
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Neoplasms
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Prostatic Disease
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Condition category
Condition code
Cancer
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Prostate
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Cancer
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Any cancer
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Cancer
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Other cancer types
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Renal and Urogenital
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Other renal and urogenital disorders
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Cancer
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Penile (penis)
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Cancer
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Testicular
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Intervention/exposure
Study type
Interventional
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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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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PSA progression free survival (PSA-PFS) at 1 year (PCWG3)
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Assessment method [1]
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PSA progression is defined as a rise in PSA by = 25% AND = 2 ng/mL above the nadir (lowest PSA point). This needs to be confirmed by a repeat PSA performed at least 3 weeks later.
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Timepoint [1]
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Date of randomisation to the date of first evidence of PSA progression at 53 weeks post randomisation.
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Secondary outcome [1]
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PSA response rate (PSA-RR)
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Assessment method [1]
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PSA response rate is defined as the proportion of participants in each group with a PSA reduction of = 50% from baseline.
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Timepoint [1]
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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.
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Secondary outcome [2]
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Frequency and severity of adverse events (CTCAE v5.0)
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Assessment method [2]
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CTCAE v5.0 will be used to measure frequency and severity of AEs during study treatment.
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Timepoint [2]
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Date of first dose of study treatment until 100 days after cessation of study treatment.
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Secondary outcome [3]
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Radiological progression free survival (PCWG3/RECIST1.1)
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Assessment method [3]
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Radiographic PFS is defined as the interval from the date of randomisation to the date of first evidence of radiographic progression, or the date of last known follow-up without progression.
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Timepoint [3]
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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.
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Secondary outcome [4]
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PSA progression free survival (PCWG3)
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Assessment method [4]
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PSA progression free survival is defined as the interval from the date of randomisation to the date of first evidence of PSA progression or the date of last known follow-up without PSA progression.
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Timepoint [4]
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Date of randomisation through to study completion, approximately 3 years from start of recruitment.
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Secondary outcome [5]
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Overall survival (OS)
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Assessment method [5]
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OS is defined as the interval from the date of randomisation to date of death from any cause, or the date of last known follow-up alive.
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Timepoint [5]
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Through to study completion, approximately 3 years from start of recruitment.
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Secondary outcome [6]
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Objective response rate (ORR)
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Assessment method [6]
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ORR is defined as partial or complete response at any stage of the study (from the date of randomisation to date of subsequent anti-cancer treatment). RECIST 1.1 will be used to assess ORR in participants with measurable disease.
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Timepoint [6]
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Date of randomisation through to study completion, approximately 3 years from start of recruitment.
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Secondary outcome [7]
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Duration of response
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Assessment method [7]
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Duration of response is defined as the interval from the date of first response (Complete Response / Partial Response as per RECIST 1.1) to the date of first documented radiological progression as per RECIST 1.1 in participants with measurable disease.
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Timepoint [7]
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Date of randomisation through to first radiological progression or through to study completion, approximately 3 years from start of recruitment.
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Secondary outcome [8]
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Time to treatment response
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Assessment method [8]
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Time to treatment response is defined as the interval from the date of randomisation to the date of first response (Complete Response / Partial Response as per RECIST 1.1) in participants with measurable disease.
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Timepoint [8]
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Date of randomisation through to study completion, approximately 3 years from start of recruitment.
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Secondary outcome [9]
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Aspects of Health Related Quality of Life (HRQoL) - 1
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Assessment method [9]
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The EORTC QLQ-C30 (European Organisation for Research on Treatment of Cancer - Quality of Life Questionnaire for cancer patients) instrument uses 28 questions about overall quality of life with each question answerable using a scale from 1 (not at all) to 4 (very much). Overall scores can be from a minimum of 28 indicating a better quality of life and higher scores with a maximum of 112 indicating lower overall quality of life. The questionnaire also has two summary questions which asks participants to rank 1) overall health and 2) overall quality of life on scale of from 1 (very poor) to 7 (excellent).
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Timepoint [9]
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Within 7 days prior to randomisation, assessed every 12 weeks, through to study completion, approximately 3 years from start of recruitment.
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Secondary outcome [10]
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Aspects of Health Related Quality of Life (HRQoL) - 2
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Assessment method [10]
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Patient DATA Form (Patient Disease and Treatment Assessment Form - 47 items) is a simple, multi-item quality of life instrument based on 11-point numeric rating scales for a range of relevant symptoms and functions. It combines cancer specific items from the UBQ-C, GLQ-8 and LASA cancer-specific quality of life instruments.
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Timepoint [10]
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Within 7 days prior to randomisation, assessed every 12 weeks, through to study completion, approximately 3 years from start of recruitment.
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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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Males
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
29/04/2022
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/12/2024
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Actual
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Sample size
Target
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Accrual to date
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Final
93
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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Recruitment hospital [1]
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St Vincents Hospital - Darlinghurst
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Recruitment hospital [2]
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Calvary Mater Newcastle - Newcastle
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Recruitment hospital [3]
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Royal Brisbane and Womens hospital - Herston
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Recruitment hospital [4]
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Royal Adelaide Hospital - Adelaide
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Recruitment hospital [5]
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Austin Health - Heidelberg
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Recruitment hospital [6]
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Peter MacCallum Cancer Centre - Melbourne
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Recruitment hospital [7]
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Alfred Hospital - Melbourne
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Recruitment hospital [8]
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Sir Charles Gairdner - Nedlands
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Recruitment postcode(s) [1]
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2010 - Darlinghurst
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Recruitment postcode(s) [2]
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2298 - Newcastle
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Recruitment postcode(s) [3]
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4029 - Herston
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Recruitment postcode(s) [4]
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5000 - Adelaide
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Recruitment postcode(s) [5]
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3084 - Heidelberg
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Recruitment postcode(s) [6]
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3000 - Melbourne
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Recruitment postcode(s) [7]
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3004 - Melbourne
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Recruitment postcode(s) [8]
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6009 - Nedlands
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Funding & Sponsors
Primary sponsor type
Other
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Name
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
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Address
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Other collaborator category [1]
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Other
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Name [1]
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Prostate Cancer Foundation of Australia
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Address [1]
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Country [1]
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Other collaborator category [2]
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Commercial sector/Industry
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Name [2]
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Bristol-Myers Squibb
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Address [2]
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Other collaborator category [3]
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Commercial sector/Industry
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Name [3]
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Advanced Accelerator Applications
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Address [3]
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Country [3]
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Other collaborator category [4]
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Other
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Name [4]
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University of Sydney
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Address [4]
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Country [4]
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Ethics approval
Ethics application status
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Summary
Brief summary
This phase II study will investigate the activity and safety of radionuclide 177Lu-PSMA
therapy versus 177Lu-PSMA in combination with Ipilimumab and Nivolumab in patients with
metastatic castrate resistant prostate cancer (mCRPC).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT05150236
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Shahneen Sandhu, MBBS, FRACP
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Address
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Peter MacCallum Cancer Centre, Australia
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT05150236
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