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

NCT ID: NCT04443062

Last Updated: 2024-10-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-20
• Study Completion Date: 2026-01-01

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Interventional arm: 177Lu-PSMA radioligand therapy

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

Group Type: EXPERIMENTAL

177Lu-PSMA-617

Intervention Type: DRUG

PSMA radioligand therapy

Standard of care

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).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

177Lu-PSMA-617

PSMA radioligand therapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Prostaatkankerstichting

UNKNOWN

Sponsor Role: collaborator

Advanced Accelerator Applications

INDUSTRY

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James Nagarajah, Prof.

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

German Oncology Center

Limassol, , Cyprus

Amsterdam UMC

Amsterdam, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Radboud University

Nijmegen, , Netherlands

Countries

Cyprus; Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 27765862 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29752180 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34736509 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32928177 (View on PubMed)

Other Identifiers

NL72585.091.20

Identifier Type: -

Identifier Source: org_study_id