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Prostate CancerPhase 2BullseyeNCT04443062

Lutetium-177-PSMA-617 in Oligo-metastatic Hormone Sensitive Prostate Cancer

A Phase 2 study testing 177Lu-PSMA-617 in people with Prostate Cancer, run by Radboud University Medical Center at 4 sites in 2 countries.

Completed

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

Official record
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Trial summary

Radioligand therapy (RLT) using Lutetium-177 labelled PSMA is a promising new therapeutic approach to treat metastatic prostate cancer. This tumor-specific treatment is directed against prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer cells. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
177Lu-PSMA-617
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
4 sitesin 2 countries
Study dates
20 Jul 2020to 1 Jan 2026
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

  • Histological proven adenocarcinoma of the prostate with sufficient archived tumor material. This material has to be archived till study closure.
  • Biochemical recurrence (PSA > 1.0 µg/l).
  • PSA-doubling time < 6 months. Serum PSA progression is defined as 2 consecutive rising PSA values measured at least 1 week apart. The minimal start value is 0.2 µg/l.
  • 18F-PSMA-PET-CT positive metastases in bones and/or lymph nodes (N1/M1ab): ≥1, maximally 5 metastases.
  • Local treatment for oligo-metastases with radiotherapy or surgery appears to be no option anymore (due to prior treatment or the location of the metastatic lesions or if the patient refuse these treatments).
  • No prior hormonal therapy (including any androgen directed treatment such as finasteride, dutasteride, bicalutamide, apalutamide, abiraterone or enzalutamide) or taxane based chemotherapy (docetaxel or cabazitaxel); testosterone > 1.7 nmol/l.
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  • Exception: local prostate cancer treated with local radiotherapy plus adjuvant ADT; these patients need to be stopped with ADT at least 6 months.
  • A detectable lesion on the 18F-PSMA PET/CT with significant PSMA avidity, defined by a SUVmax > 15 (partial volume corrected).
  • ECOG 0-1
  • Patients must have a life expectancy >6 months.
  • Laboratory values:
  • White blood cells > 3.0 x 109/l
  • Platelet count > 75 x 109/l
  • Hemoglobin > 6.2 mmol/l
  • ASAT, ALAT < 3 x ULN
  • MDRD-GFR ≥ 50 ml/min
  • Signed informed consent.

Who cannot join

  • A known subtype other than prostate adenocarcinoma.
  • Previous PSMA based radioligand treatment.
  • Visceral or brain metastases.
  • Any medical condition present that in the opinion of the investigator will affect patients' clinical status when participating in this trial.
  • Prior hip replacement surgery potentially influencing performance of PSMA PET/CT.
  • Sjogren's syndrome
  • A second active malignancy other than prostate cancer.
  • Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception.

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

Netherlands3 sites

  • Amsterdam UMC

    Amsterdam

  • University Medical Center Groningen

    Groningen

  • Radboud University

    Nijmegen

Other trials in Netherlands

Cyprus1 site

  • German Oncology Center

    Limassol

Other trials in Cyprus

About this study

Official title: Lutetium-177-PSMA-617 Radioligand Therapy in Oligo-metastatic Hormone Sensitive Prostate Cancer.

Radioligand therapy (RLT) using Lutetium-177 labelled PSMA is a promising new therapeutic approach to treat metastatic prostate cancer. This tumor-specific treatment is directed against prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer cells. In the last few years, several lutetium-177 (177Lu, β emitter) labeled PSMA ligands have been developed and are currently applied to treat metastatic castrate resistant prostate cancer patients. To date, there are no prospective randomized studies published using this treatment in the hormone sensitive setting or in oligometastatic prostate cancer. Therefore, this study we will evaluate the effect of 177Lu-PSMA in patients with hormone sensitive oligo-metastatic prostate cancer.

Read the detailed description

Prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a promising new therapeutic approach to treat metastatic prostate cancer. This tumor-specific treatment is directed against PSMA, which is overexpressed in prostate cancer cells. In the last few years, several Lutetium-177 (177Lu, β emitter) labeled PSMA ligands have been developed and are currently applied in nuclear medicine departments worldwide to treat metastatic castrate resistant prostate cancer (mCRPC) patients.

A large retrospective study reported an overall biochemical response rate of 45% following multiple 177Lu-PSMA RLT cycles in mCRPC patients, while 40% of patients already responded after a single cycle. RLT with 177Lu-PSMA was generally well tolerated and 12% of the patients suffered grade 3 to 4 hematological toxicity. In addition, mild and often transient xerostomia occurred in 8%. A prospective study carried out in Australia confirmed these results recently. Based on these outcomes Endocyte (a Novartis company) is currently carrying out an international multicenter prospective registration study for end-stage mCRPC patients (NCT03511664).

Although these results are promising, it is noteworthy that most of the currently available data is retrospective and 177Lu-PSMA has only been evaluated in end stage prostate cancer patients to date. However, based on the mode of action, 177Lu-PSMA could also be effective in low volume disease because of the very high tumor uptake of radioligands in smaller lesions. Also, in a pilot study (NCT03828838) we were able to show that 177Lu-PSMA treatment is safe coupled with promising response rates. Hence, the present randomized trial to investigate the efficacy of 177Lu-PSMA in patients with oligo-metastatic (≤5 metastases) metastatic prostate cancer, prior to the hormone insensitive state. In this study, 58 patients will be included in a 1:1 ratio to receive either 177Lu-PSMA or the current standard of care (deferred androgen deprivation therapy).

At the end of the study period for answering the primary research question, patients randomized to the control arm are eligible to receive 177Lu-PSMA if they meet the end of the study period treatment (EOT 1) criteria and are willing to undergo 177Lu-PSMA.

EOT 1 is defined by:

  • Clinical progression determined by the treating physician (e.g. increasing pain from metastases)
  • A 100% increase in PSA after cycle one blood draw (BASELINE) during study. Exception: PSA increase in the first 12 weeks after the first treatment injection as was defined by the PCWG3 criteria.
Conditions
Prostate Cancer
Being tested
177Lu-PSMA-617
Keywords
Prostate cancer, Hormone sensitive, Oligometastases, 177Lu-PSMA, Metastases directed therapy
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • 177Lu-PSMA-617Drug

    PSMA radioligand therapy

Study groups in NCT04443062
Study groupRoleWhat they receive
Interventional arm: 177Lu-PSMA radioligand therapyExperimental2 (+2) cycles of 7.4 GBq 177Lu-PSMA 6 weeks in between
Receives: Drug: 177Lu-PSMA-617
Standard of careNo interventionDeferred androgen deprivation therapy. However, the control arm can receive the study drug (177Lu-PSMA) in case of disease progression (defined in the study protocol).

What is being measured

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

  1. To compare the fraction of patients that have disease progression (and meet EOT 1) criteria within 6 months in a group of patients that are treated with 177Lu-PSMA and a group that follows the current standard of care.

    Disease progression (EOT 1) is defined by:

    • A 100% increase in PSA after cycle one blood draw (BASELINE) during study. Exception: PSA increase in the first 12 weeks after the first treatment injection as was defined by the PCWG3 criteria. Or;
    • Clinical progression determined by the treating physician (e.g. increasing pain from metastases).

    Measured: 30 weeks

  2. A second primary aim is to compare the two arms for the time to disease progression and meeting EOT 1 criteria.

    Disease progression (EOT 1) is defined by:

    • A 100% increase in PSA after cycle one blood draw (BASELINE) during study. Exception: PSA increase in the first 12 weeks after the first treatment injection as was defined by the PCWG3 criteria. Or;
    • Clinical progression determined by the treating physician (e.g. increasing pain from metastases).

    Measured: 30 weeks

Secondary outcomes (7)

  1. To evaluate the clinical efficacy of multiple doses 177Lu-PSMA radioligand therapy in patients with oligo-metastatic, hormone sensitive metastatic PCa by:

    The change in PSA after 177Lu-PSMA and proportion of achieving a ≥ 50% decrease in PSA from baseline.

    Measured: 30 weeks

  2. To evaluate the clinical efficacy of multiple doses 177Lu-PSMA radioligand therapy in patients with oligo-metastatic, hormone sensitive metastatic PCa by:

    The changes in uptake (SUVmax) of 18F-PSMA PET/CT before and 6 months after 177Lu-PSMA.

    Measured: 30 weeks

  3. To evaluate the clinical efficacy of multiple doses 177Lu-PSMA radioligand therapy in patients with oligo-metastatic, hormone sensitive metastatic PCa by:

    The size of soft tissue metastases on 18F-PSMA PET/CT and (whole body) MRI after 177Lu-PSMA.

    Measured: 30 weeks

  4. Progression free survival defined as from the time from inclusion to date of evidence of clinical progression, death from any cause, PSA progression, or radiographic progression.

    Clinical progression is defined by the treating physician (e.g. increasing pain from metastases). PSA progression is defined as a ≥ 25% increase in PSA from nadir, with a minimum PSA of >0,5 µg/l and which is confirmed by a second value ≥ 3 weeks later (i.e. confirmed rising trend). Within the first 12 weeks after treatment administration PSA increases will be ignored in the absence of other evidence of disease progression due to the flare phenomenon. If no decline occurs, date of ≥ 25% increase will be recorded. Radiographic progression is defined by the amount and size of the lesions. Where applicable PCWG3 and RECIST v1.1 criteria will be followed.

    Measured: 30 weeks

  5. Time till initiation of ADT in patients receiving 177Lu-PSMA. ADT free survival is defined by the date any ADT (e.g. bicalutamide, LHRH, enzalutamide, abiraterone, etc.) is started or death related to PCa.

    Measured: 30 weeks

  6. To evaluate the tolerability and toxicity of 177Lu-PSMA defined by NCI Common Terminology Criteria for Adverse Events v5.0.

    Measured: 30 weeks

  7. To evaluate the quality of life before and up to 6 months after 177Lu-PSMA RLT.

    The following questionnaires will be used: EORTC QLQ-C30, QLQ-PR25 \& xerostomia inventory.

    Measured: 30 weeks

Timeline

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

  1. First posted23 Jun 2020
  2. Study start20 Jul 2020
  3. Primary completion1 Apr 2025
  4. Study completion1 Jan 2026

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
Randomized, two-arm, open label, multi-center, phase II study
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04443062
Sponsor's protocol ID
NL72585.091.20
Acronym
Bullseye
Status last verified
Sep 2024
First submitted
17 Jun 2020
Last updated
27 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Rahbar K, Ahmadzadehfar H, Kratochwil C, Haberkorn U, Schafers M, Essler M, Baum RP, Kulkarni HR, Schmidt M, Drzezga A, Bartenstein P, Pfestroff A, Luster M, Lutzen U, Marx M, Prasad V, Brenner W, Heinzel A, Mottaghy FM, Ruf J, Meyer PT, Heuschkel M, Eveslage M, Bogemann M, Fendler WP, Krause BJ. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. J Nucl Med. 2017 Jan;58(1):85-90. doi: 10.2967/jnumed.116.183194. Epub 2016 Oct 20.

    PubMed 27765862

  • Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, Iravani A, Kong G, Ravi Kumar A, Murphy DG, Eu P, Jackson P, Scalzo M, Williams SG, Sandhu S. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018 Jun;19(6):825-833. doi: 10.1016/S1470-2045(18)30198-0. Epub 2018 May 8.

    PubMed 29752180

  • Prive BM, Noordzij W, Muselaers CHJ, de Jong IJ, van Oort IM, Janssen MJR, Van Rijk MC, van Gemert WA, Timmermans B, de Groot M, Mehra N, Gerritsen WR, Jonker MA, Alevroudis E, van der Gaag S, Koppes JCC, Sedelaar JPM, Vis AN, Vrachimis A, Oprea-Lager DE, Nagarajah J. [177Lu]-PSMA-617-PSMA-617 in oligometastatic hormone sensitive prostate cancer (BULLSEYE): an open-label, randomised, phase 2 study. Lancet Oncol. 2026 Apr;27(4):461-469. doi: 10.1016/S1470-2045(25)00762-4.

    PubMed 41926960

  • Prive BM, Janssen MJR, van Oort IM, Muselaers CHJ, Jonker MA, van Gemert WA, de Groot M, Westdorp H, Mehra N, Verzijlbergen JF, Scheenen TWJ, Zamecnik P, Barentsz JO, Gotthardt M, Noordzij W, Vogel WV, Bergman AM, van der Poel HG, Vis AN, Oprea-Lager DE, Gerritsen WR, Witjes JA, Nagarajah J. Update to a randomized controlled trial of lutetium-177-PSMA in Oligo-metastatic hormone-sensitive prostate cancer: the BULLSEYE trial. Trials. 2021 Nov 4;22(1):768. doi: 10.1186/s13063-021-05733-4.

    PubMed 34736509

  • Prive BM, Janssen MJR, van Oort IM, Muselaers CHJ, Jonker MA, de Groot M, Mehra N, Verzijlbergen JF, Scheenen TWJ, Zamecnik P, Barentsz JO, Gotthardt M, Noordzij W, Vogel WV, Bergman AM, van der Poel HG, Vis AN, Oprea-Lager DE, Gerritsen WR, Witjes JA, Nagarajah J. Lutetium-177-PSMA-I&T as metastases directed therapy in oligometastatic hormone sensitive prostate cancer, a randomized controlled trial. BMC Cancer. 2020 Sep 14;20(1):884. doi: 10.1186/s12885-020-07386-z.

    PubMed 32928177

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 177Lu-PSMA-617 in people with Prostate Cancer, run by Radboud University Medical Center at 4 sites in 2 countries.

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 17 inclusion and 8 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 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Netherlands, Cyprus. 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?

To compare the fraction of patients that have disease progression (and meet EOT 1) criteria within 6 months in a group of patients that are treated with 177Lu-PSMA and a group that follows the current standard of care. (time frame: 30 weeks). The study lists 2 primary outcomes in all. 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 NCT04443062, which also lists 5 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 27 Feb 2026.

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