AzTrials
AzTrials

Cancer of the ProstatePhase 2TheraPNCT03392428

A Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer

A Phase 2 study testing 177Lu-PSMA617 and Cabazitaxel in people with Cancer of the Prostate and Metastatic Cancer, run by Australian and New Zealand Urogenital and Prostate Cancer Trials Group at 11 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Cancer of the Prostate, Metastatic Cancer
What is being tested?
177Lu-PSMA617 and Cabazitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
201 participants
Where
11 sitesAustralia
Study dates
29 Jan 2018to 31 Dec 2021
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

  • 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)
  • Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing Luteinizing Hormone-Releasing Hormone (LHRH) analog
  • Progressive disease with rising PSA on 3 consecutive measurements, and PSA ≥ 20 ng/mL
  • Target or non-target lesions according to RECIST 1.1
Show all 23Show fewer
  • Prior treatment with docetaxel
  • 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)
  • ECOG Performance status 0 to 2
  • Assessed by a medical oncologist as suitable for chemotherapy with cabazitaxel
  • Adequate renal function:
  • Cr Cl ≥ 40mL/min (Cockcroft-Gault formula)
  • 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
  • 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)
  • Estimated life expectancy > 12 weeks
  • Study treatment both planned and able to start within 21 days of randomisation
  • 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
  • Signed, written informed consent

Who cannot join

  • Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
  • Site(s) of disease that are FDG positive with minimal PSMA expression defined as FDG intensity > 68Ga-PSMA activity OR 68Ga-PSMA SUVmax < 10
  • Sjogren's syndrome
  • Prior treatment with cabazitaxel or Lu-PSMA
  • Contraindications to the use of corticosteroid treatment
  • Active malignancy other than prostate cancer
Show all 9Show fewer
  • Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
  • 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
  • Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Australia11 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Royal Brisbane and Womens Hospital

    Brisbane, Queensland, 4029

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3008

  • Austin Hospital

    Melbourne, Victoria, 3084

  • Monash Moorabbin Hospital

    Moorabbin, Victoria, 3165

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6450

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • St Vincent's Hospital

    Sydney, New South Wales, 2010

  • Royal North Shore Hospital

    Sydney, New South Wales, 2065

  • Calvary Mater Newcastle Hospital

    Waratah, New South Wales, 2298

Other trials in Australia

About this study

Official title: TheraP: A Randomised Phase 2 Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer (ANZUP Protocol 1603)

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

Read the detailed description

Despite recent advances in the treatment of prostate cancer, metastatic disease remains incurable.

Prostate specific membrane antigen (PSMA) is present in high quantities on the cell surface of prostate cancers, and is also further increased in metastatic hormone refractory carcinomas. PSMA is an attractive target for both imaging and treatment of prostate cancer. PSMA bound to the radioactive substance Gallium68 (GaPSMA) is rapidly being adopted for imaging prostate cancer using positron emission tomography (PET) scanning.

Radionuclide therapy is an approach for the treatment of cancer that uses tumour targeting agents to deliver high doses of radiation to sites of tumours. The PSMA molecule used for PET imaging can also be labelled with Lutetium177 (Lu177), a radioactive substance.

The aim of this study is to determine the activity and safety of LuPSMA radionuclide therapy.

Patients with metastatic prostate cancer who have progressed despite hormonal therapy and chemotherapy, will be randomised to receive either LuPSMA radionuclide therapy (up to a maximum of 6 cycles of therapy) or cabazitaxel chemotherapy (up to a maximum of 10 cycles of therapy).

200 participants will be recruited from sites across Australia.

The study will determine the effects on PSA response rate (primary endpoint), pain response, progression free survival, quality of life, and frequency and severity of adverse events. Correlative outcomes include associations between PET imaging and clinical outcomes, and biomarkers and clinical outcomes.

Being tested
177Lu-PSMA617, Cabazitaxel
Medical subject headings
Prostatic Neoplasms, Neoplasm Metastasis

What participants receive

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

  • 177Lu-PSMA617Other

    Also called Lutetium Prostate-specific membrane antigen

    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.

  • CabazitaxelDrug

    Also called Jevtana

    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.

Study groups in NCT03392428
Study groupRoleWhat they receive
177Lu-PSMA617ExperimentalPatients 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.
Receives: Other: 177Lu-PSMA617
CabazitaxelActive comparatorPatients 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.
Receives: Drug: Cabazitaxel

What is being measured

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

  1. 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.

    Measured: Through study completion, on average 4 years

Secondary outcomes (9)

  1. 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)

    Measured: Through study completion, on average 4 years

  2. 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).

    Measured: Through study completion, on average 4 years

  3. 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

    Measured: Through study completion, on average 4 years

  4. 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.

    Measured: Through study completion, on average 4 years

  5. 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).

    Measured: Through study completion, on average 4 years

  6. 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).

    Measured: Through study completion, on average 4 years

  7. 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).

    Measured: Through study completion, on average 4 years

  8. Overall survival

    Overall survival - time from registration to death from any cause or last known follow-up alive.

    Measured: Through study completion, on average 4 years

  9. Frequency and severity of adverse events

    Frequency and severity of adverse events (composite), assessed using CTCAE v4.03.

    Measured: From first study dose to 12 weeks after completing study treatment

Timeline

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

  1. First posted8 Jan 2018
  2. Study start29 Jan 2018
  3. Primary completion31 Dec 2019
  4. Study completion31 Dec 2021

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
Model description
Open label, randomised, stratified, 2-arm, phase 2 trial
Masking
None (open label)
Enrolment
201 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03392428
Sponsor's protocol ID
ANZUP 1603
Acronym
TheraP
Status last verified
Jun 2022
First submitted
11 Dec 2017
Last updated
13 Jun 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Kwan EM, Ng SWS, Tolmeijer SH, Emmett L, Sandhu S, Buteau JP, Iravani A, Joshua AM, Francis RJ, Subhash V, Lee ST, Scott AM, Martin AJ, Stockler MR, Donnellan G, Annala M, Herberts C, Davis ID, Hofman MS, Azad AA, Wyatt AW; TheraP Investigators and the ANZUP Cancer Trials Group. Lutetium-177-PSMA-617 or cabazitaxel in metastatic prostate cancer: circulating tumor DNA analysis of the randomized phase 2 TheraP trial. Nat Med. 2025 Aug;31(8):2722-2736. doi: 10.1038/s41591-025-03704-9. Epub 2025 May 27.

    PubMed 40425844

  • Hofman MS, Emmett L, Sandhu S, Iravani A, Buteau JP, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, Stockler MR, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial. Lancet Oncol. 2024 Jan;25(1):99-107. doi: 10.1016/S1470-2045(23)00529-6. Epub 2023 Nov 30.

    PubMed 38043558

  • Viljoen B, Hofman MS, Chambers SK, Dunn J, Dhillon HM, Davis ID, Ralph N. Experiences of participants in a clinical trial of a novel radioactive treatment for advanced prostate cancer: A nested, qualitative longitudinal study. PLoS One. 2022 Nov 9;17(11):e0276063. doi: 10.1371/journal.pone.0276063. eCollection 2022.

    PubMed 36350899

  • Buteau JP, Martin AJ, Emmett L, Iravani A, Sandhu S, Joshua AM, Francis RJ, Zhang AY, Scott AM, Lee ST, Azad AA, McJannett MM, Stockler MR, Williams SG, Davis ID, Hofman MS; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. PSMA and FDG-PET as predictive and prognostic biomarkers in patients given [177Lu]Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): a biomarker analysis from a randomised, open-label, phase 2 trial. Lancet Oncol. 2022 Nov;23(11):1389-1397. doi: 10.1016/S1470-2045(22)00605-2. Epub 2022 Oct 16.

    PubMed 36261050

  • Viljoen B, Hofman MS, Chambers SK, Dunn J, Dhillon H, Davis ID, Ralph N. Advanced prostate cancer experimental radioactive treatment-clinical trial decision making: patient experiences. BMJ Support Palliat Care. 2021 Aug 9:bmjspcare-2021-002994. doi: 10.1136/bmjspcare-2021-002994. Online ahead of print.

    PubMed 34373282

  • Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 27;397(10276):797-804. doi: 10.1016/S0140-6736(21)00237-3. Epub 2021 Feb 11.

    PubMed 33581798

  • Iravani A, Violet J, Azad A, Hofman MS. Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies. Prostate Cancer Prostatic Dis. 2020 Mar;23(1):38-52. doi: 10.1038/s41391-019-0174-x. Epub 2019 Oct 8.

    PubMed 31595044

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 177Lu-PSMA617 and Cabazitaxel in people with Cancer of the Prostate and Metastatic Cancer, run by Australian and New Zealand Urogenital and Prostate Cancer Trials Group at 11 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 23 inclusion and 9 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: finished, as of the sponsor's last update on 13 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Prostate Specific Antigen response rate (PSA RR) (time frame: Through study completion, on average 4 years). 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 NCT03392428, which also lists 7 linked publications.

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 13 Jun 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in