NCT04443062

Brief 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. 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
58

participants targeted

Target at P50-P75 for phase_2 prostate-cancer

Timeline
Completed

Started Jul 2020

Typical duration for phase_2 prostate-cancer

Geographic Reach
2 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 17, 2020

Completed
6 days until next milestone

First Posted

Study publicly available on registry

June 23, 2020

Completed
27 days until next milestone

Study Start

First participant enrolled

July 20, 2020

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2025

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2026

Completed
Last Updated

February 27, 2026

Status Verified

September 1, 2024

Enrollment Period

4.7 years

First QC Date

June 17, 2020

Last Update Submit

February 24, 2026

Conditions

Prostate Cancer

Keywords

Prostate cancerHormone sensitiveOligometastases177Lu-PSMAMetastases directed therapy

Outcome Measures

Primary Outcomes (2)

  • 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).

    30 weeks

  • 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).

    30 weeks

Secondary Outcomes (7)

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

    30 weeks

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

    30 weeks

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

    30 weeks

  • 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.

    30 weeks

  • 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.

    30 weeks

  • +2 more secondary outcomes

Study Arms (2)

Interventional arm: 177Lu-PSMA radioligand therapy

EXPERIMENTAL

2 (+2) cycles of 7.4 GBq 177Lu-PSMA 6 weeks in between

Drug: 177Lu-PSMA-617

Standard of care

NO INTERVENTION

Deferred androgen deprivation therapy. However, the control arm can receive the study drug (177Lu-PSMA) in case of disease progression (defined in the study protocol).

Interventions

177Lu-PSMA-617DRUG

PSMA radioligand therapy

Interventional arm: 177Lu-PSMA radioligand therapy

Eligibility Criteria

Age18 Years+
Sexmale(Gender-based eligibility)
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • F-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.
  • 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
  • +2 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

German Oncology Center

Limassol, Cyprus

Location

Amsterdam UMC

Amsterdam, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Radboud University

Nijmegen, Netherlands

Location

Related Publications (4)

  • 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.

    PMID: 27765862BACKGROUND

  • 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.

    PMID: 29752180BACKGROUND

  • 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.

    PMID: 34736509DERIVED

  • 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.

    PMID: 32928177DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pluvicto

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Study Officials

  • James Nagarajah, Prof.

    Radboud University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Randomized, two-arm, open label, multi-center, phase II study
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 17, 2020

First Posted

June 23, 2020

Study Start

July 20, 2020

Primary Completion

April 1, 2025

Study Completion

January 1, 2026

Last Updated

February 27, 2026

Record last verified: 2024-09

Locations

CY(1)NL(3)