DUET-study: a Feasibility Study of 177LU-PSMA Radioligand Therapy Alternated with RADIUM-223 in Patients with Bone-Metastatic, Oligo-Metastatic Hormone-Sensitive Prostate Cancer After Curative Therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

21 Nov 2024 → 2 Apr 2026

Decision date (initial)

2024-12-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amsterdam UMC · Bayer BV

External identifiers

EU CT number

2024-518985-29-02

EudraCT number

2022-002022-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The primary objective of this study is to assess the feasibility and safety of drug application in patients with bone metastatic, oligometastatic, hormone sensitive prostate cancer after curative therapy treated by Radium-223 radioligand therapy (RLT) alternated with 177Lu-PSMA RLT.

Secondary objectives 4

1. To study the tolerability (toxicity) of study medication (i.e., Ra-223 RLT and 177Lu-PSMA RLT).
2. To assess the health-related quality of life (HRQoL) and xerostomia by patient reported outcome measures (PROMS) and specific QoL questionnaires, using RAND-36 and the xerostomia inventory, at baseline and repeatedly each two weeks after initiation of treatment and after the last treatment.
3. To assess the PSA free survival at 3,6 and 12 months after combined cytotoxic RLT, i.e., 177Lu-PSMA RLT alternated with Radium-223 RLT.
4. To assess the radiological response on PSMA PET/CT, bone scan and diagnostic CT abdomen and thorax performed three months after last treatment

Conditions and MedDRA coding

Prostate cancer

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Histological proven adenocarcinoma of the prostate
2. Previous curative therapy with a radical prostatectomy or external-beam radiotherapy (EBRT)
3. Biochemical recurrence
4. Serum PSA progression
5. PSMA expressing metastases on an 18F‐PSMA‐PET‐CT scan: bone (and/or lymph node metastases) (miN1/miM1ab): minimally 1 bone metastases, maximally 5 bone metastases
6. 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 refuses these treatments)
7. No prior hormonal therapy (including any androgen directed treatment such as finasteride, dutasteride, bicalutamide, apalutamide, abiraterone, enzalutamide, and darolutamide) or taxane based chemotherapy (docetaxel or cabazitaxel)
8. Testosterone > 1.7 nmol/l (at baseline within 4 weeks before start of therapy)
9. A detectable lesion on the 18F‐PSMA PET/CT (at baseline within 4 weeks before start of therapy)
10. ECOG 0‐1
11. Patients must have a life expectancy >12 months
12. Laboratory values (at baseline within 4 weeks before start of therapy ): • White blood cells > 4.0 x 109/l • Platelet count > 150 x 109/l • Hemoglobin > 7.0 mmol/l • MDRD‐GFR ≥ 60 ml/min
13. Signed informed consent.

Exclusion criteria 7

1. A known subtype other than prostate adenocarcinoma
2. Previous radioligand treatment
3. Visceral (liver/lung) or brain metastases
4. Any medical condition that in the opinion of the investigator will negatively affect patients’ clinical status when participating in this trial
5. Prior hip replacement surgery potentially influencing performance of PSMA PET/CT
6. Sjögrens syndrome
7. A second active malignancy other than prostate cancer

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The feasibility and safety of drug application in patients with bone metastatic, oligometastatic, HSPCa after curative therapy (i.e., radical prostatectomy) treated by alternated Radium-223 RLT and 177Lu-PSMA RLT.
2. The proposed treatment schedule is considered unfeasible when treatment is postponed more than 4 weeks in more than 50% of participants due to treatment related toxicity (myelosuppression or xerostomia), or when treatment had to be cancelled due to unwillingness of patients to continue (or complete) treatment.

Secondary endpoints 4

1. The tolerability (toxicity) of study medication (i.e., Ra-223 RLT and 177Lu-PSMA RLT)
2. the health-related quality of life (HRQoL) and the incidence of xerostomia by patient reported outcome measures (PROMS) using the RAND-36 and the xerostomia inventory, at baseline and repeatedly each two weeks after initiation of 177Lu-PSMA RLT and after the last treatment.
3. the prostate-specific antigen (PSA) free survival at 3,6 and 12 months after combined cytotoxic RLT, i.e., 177Lu-PSMA RLT and Radium-223 RLT.
4. the radiological response on PSMA PET/CT, bone scan and CT abdomen and thorax performed three months after last treatment (± 3 weeks).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Investigator

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Investigator

Sponsor responsibilities

Article 77 compliance

Amsterdam UMC Stichting

Contact point sponsor

Amsterdam UMC Stichting

Article 77 implementation

Amsterdam UMC Stichting

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications