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Prostatic NeoplasmsPhase 2ANZUP2001NCT05150236

EVOLUTION: 177Lu-PSMA Therapy Versus 177Lu-PSMA in Combination With Ipilimumab and Nivolumab for Men With mCRPC

A Phase 2 study testing 177Lu-PSMA-617, Ipilimumab and Nivolumab in people with Prostatic Neoplasms and Genital Neoplasms, Male, run by Australian and New Zealand Urogenital and Prostate Cancer Trials Group at 8 sites in Australia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
177Lu-PSMA-617, Ipilimumab and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
93 participants
Where
8 sitesAustralia
Study dates
29 Apr 2022to Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged 18 years or older, with histologically confirmed adenocarcinoma of the prostate.
  • Castration-resistant metastatic prostate cancer (defined as disease progressing despite castration by orchidectomy or ongoing luteinising hormone-releasing hormone agonist or antagonist).
  • 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
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  • Target or non-target lesions according to RECIST 1.1 and PCWG3
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • 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)
  • Patients must have a life expectancy ≥ 24 weeks.
  • Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
  • Signed, written informed consent.

Who cannot join

  • Prostate cancer with known significant sarcomatoid, spindle cell or neuroendocrine cell components, or metastasis of other cancers to the prostate.
  • 18F-FDG-PET/CT SUVmax ≥10 at a site of measurable disease with no concurrent PSMA expression > 10mm
  • 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.
  • 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.
  • Prior treatment with 177Lu-PSMA.
  • 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.
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  • 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.
  • Participants must have recovered from all AE due to previous therapies to ≤Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible.
  • 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.
  • Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated.
  • Radiation or surgery within 2 weeks of randomisation.
  • Previous history of interstitial lung disease or non-infectious pneumonitis.
  • Administration of a live vaccine within 30 days prior to the first dose of study drug.
  • 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.
  • Inadequate contraception. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Australia8 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • St Vincents Hospital

    Darlinghurst, New South Wales, 2010

  • Austin Health

    Heidelberg, Victoria, 3084

  • Royal Brisbane and Womens hospital

    Herston, Queensland, 4029

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

  • Alfred Hospital

    Melbourne, Victoria, 3004

  • Sir Charles Gairdner

    Nedlands, Western Australia, 6009

  • Calvary Mater Newcastle

    Newcastle, New South Wales, 2298

Other trials in Australia

About this study

Official 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)

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).

Read the detailed description

This is an open label, randomised, stratified, multicentre phase 2 clinical trial recruiting 110 participants over 18 months and followed for 12 months. Participants will be randomised to 177Lu-PSMA in combination with Ipilimumab and Nivolumab and 177Lu-PSMA alone in a 2:1 ratio (using minimisation with a random component) stratified by prior exposure to docetaxel.

Being tested
177Lu-PSMA-617, Ipilimumab, Nivolumab
Medical subject headings
Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Prostatic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 177Lu-PSMA-617Drug

    Also called 177Lutetium -PSMA 617 also referred to as 177Lu-PSMA

    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.

  • IpilimumabDrug

    Also called YERVOY

    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.

  • NivolumabDrug

    Also called OPDIVO

    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.

Study groups in NCT05150236
Study groupRoleWhat they receive
Combination 177Lu-PSMA-617, Ipilimumab & NivolumabExperimental177Lu-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.
Receives: Drug: 177Lu-PSMA-617; Drug: Ipilimumab; Drug: Nivolumab
177Lu-PSMA-617Experimental177Lu-PSMA (7.5GBq) given every 6 weeks up to 6 cycles or until disease progression or unacceptable toxicity.
Receives: Drug: 177Lu-PSMA-617

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PSA progression free survival (PSA-PFS) at 1 year (PCWG3)

    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.

    Measured: Date of randomisation to the date of first evidence of PSA progression at 53 weeks post randomisation.

Secondary outcomes (10)

  1. PSA response rate (PSA-RR)

    PSA response rate is defined as the proportion of participants in each group with a PSA reduction of ≥ 50% from baseline.

    Measured: 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.

  2. Frequency and severity of adverse events (CTCAE v5.0)

    CTCAE v5.0 will be used to measure frequency and severity of AEs during study treatment.

    Measured: Date of first dose of study treatment until 100 days after cessation of study treatment.

  3. Radiological progression free survival (PCWG3/RECIST1.1)

    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.

    Measured: 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.

  4. PSA progression free survival (PCWG3)

    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.

    Measured: Date of randomisation through to study completion, approximately 3 years from start of recruitment.

  5. Overall survival (OS)

    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.

    Measured: Through to study completion, approximately 3 years from start of recruitment.

  6. Objective response rate (ORR)

    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.

    Measured: Date of randomisation through to study completion, approximately 3 years from start of recruitment.

  7. Duration of response

    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.

    Measured: Date of randomisation through to first radiological progression or through to study completion, approximately 3 years from start of recruitment.

  8. Time to treatment response

    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.

    Measured: Date of randomisation through to study completion, approximately 3 years from start of recruitment.

  9. Aspects of Health Related Quality of Life (HRQoL) - 1

    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).

    Measured: Within 7 days prior to randomisation, assessed every 12 weeks, through to study completion, approximately 3 years from start of recruitment.

  10. Aspects of Health Related Quality of Life (HRQoL) - 2

    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.

    Measured: Within 7 days prior to randomisation, assessed every 12 weeks, through to study completion, approximately 3 years from start of recruitment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2021
  2. Study start29 Apr 2022
  3. Primary completion31 Aug 2024 (estimated)
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
93 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05150236
Sponsor's protocol ID
ANZUP 2001
Acronym
ANZUP2001
Status last verified
Dec 2023
First submitted
30 Sep 2021
Last updated
15 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 177Lu-PSMA-617, Ipilimumab and Nivolumab in people with Prostatic Neoplasms and Genital Neoplasms, Male, run by Australian and New Zealand Urogenital and Prostate Cancer Trials Group at 8 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 15 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PSA progression free survival (PSA-PFS) at 1 year (PCWG3) (time frame: Date of randomisation to the date of first evidence of PSA progression at 53 weeks post randomisation.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05150236.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2023.

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