EBRT + Lu-PSMA for N1M0 Prostate Cancer

NCT05162573 | Completed Phase 1

• 3 other identifiers: M21PQ12020-005577-27NL75976.031.21
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

The PROQURE project aims to provide prostate cancer patients with more cure and better quality of life. The first part of this project (PROQURE-1) aims to explore an innovative combined modality treatment strategy for patients with node-positive prostate cancer (N1M0). The current standard of care for these patients, external beam radiotherapy (EBRT) of the prostate and regional pelvic nodes combined with 2-3 years androgen deprivation therapy (ADT), leads to suboptimal tumor control while inducing significant and potentially persistent toxicity. To overcome this, the current locoregional treatment is complemented with systemic Lutetium-177-PSMA radioligand therapy in a phase I study, with the aim to achieve better tumor control while potentially reducing or obviating ADT and its associated toxicity for future patients.

Conditions

Prostatic Neoplasm

Keywords

Lu-PSMA; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  The maximum tolerated dose (MTD) of the 4 selected doses of Lu-PSMA (3, 6, 9 and 2x7.4 GBq) when administered in combination with EBRT.

  from start of EBRT until 3 months after EBRT

Secondary Outcomes (3)

• Dose-limiting-toxicity (DLT)

  From start of EBRT until 3 months after EBRT

• Late toxicity

  6 months after EBRT

• Anti-tumor efficacy

  6 months after EBRT

Study Arms (4)

EBRT + 3 GBq Lu-PSMA

EXPERIMENTAL

Drug: 177Lu-PSMA-617; Radiation: EBRT

EBRT + 6 GBq Lu-PSMA

EXPERIMENTAL

Drug: 177Lu-PSMA-617; Radiation: EBRT

EBRT + 9 GBq Lu-PSMA

EXPERIMENTAL

Drug: 177Lu-PSMA-617; Radiation: EBRT

EBRT + 2x7.4 GBq Lu-PSMA

EXPERIMENTAL

Drug: 177Lu-PSMA-617; Radiation: EBRT

Interventions

177Lu-PSMA-617 DRUG

Dose-escalation of 177Lu-PSMA-617 (3, 6, 9 or 2x7.4 GBq) combined with external beam radiotherapy (EBRT)

EBRT + 2x7.4 GBq Lu-PSMA; EBRT + 3 GBq Lu-PSMA; EBRT + 6 GBq Lu-PSMA; EBRT + 9 GBq Lu-PSMA

EBRT RADIATION

External Beam Radiotherapy

EBRT + 2x7.4 GBq Lu-PSMA; EBRT + 3 GBq Lu-PSMA; EBRT + 6 GBq Lu-PSMA; EBRT + 9 GBq Lu-PSMA

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven prostate cancer;
• cT2-4, partly determined by MRI;
• N1, determined by LND/SNP and/or PSMA PET/CT;
• iM0, determined by PSMA PET/CT;
• Accepted for curative intent treatment with EBRT of the prostate and regional nodes + 3y ADT;
• Visually PSMA-positive primary tumor and nodes, largest lesion ≥ average liver uptake;
• WHO performance score 0-1;
• Age \> 18 years;
• For patients who have partners of childbearing potential: Willingness to use a method of birth control with adequate barrier protection during the study and for 6 months after the study drug administration; and
• Signed written informed consen

You may not qualify if:

• Inability to comply to study procedures;
• Inability to adhere to radiation safety measures in hospital or at home;
• Inability to undergo the required biodistribution scans;
• Prior or current malignant disease with potential impact on treatment outcome or survival;
• Prior treatment with EBRT;
• Prior treatment with ADT, already initiated \>1 month before the start of EBRT;
• Prior treatment with radionuclide therapies, 177Lu-PSMA-617 or other;
• Reduced bone marrow reserve (Hb\<6 mmol/L, Leukocytes\<2.5 10E9/L, or Platelets\<100 10E9/L not older than 1 month before start of EBRT);
• Reduced renal function (GFR \< 60 not older than 1 month before start of EBRT);
• Reduced salivary gland function (history of prior salivary gland disease); or
• Miction problems requiring pre-treatment with ADT.

Sponsors & Collaborators

• UMC Utrecht: collaborator
• Advanced Accelerator Applications: collaborator
• The Netherlands Cancer Institute: lead

Study Sites (2)

Netherlands Cancer Institute

Amsterdam, 1066 CX, Netherlands

Location

UMC Utrecht

Utrecht, 3508 GA, Netherlands

Location

Related Publications (1)

• van der Sar ECA, Braat AJAT, van der Voort-van Zyp JRN, van der Veen BS, van Leeuwen PJ, de Vries-Huizing DMV, Hendrikx JMA, Lam MGEH, Vogel WV. Tolerability of concurrent external beam radiotherapy and [177Lu]Lu-PSMA-617 for node-positive prostate cancer in treatment naive patients, phase I study (PROQURE-I trial). BMC Cancer. 2023 Mar 23;23(1):268. doi: 10.1186/s12885-023-10725-5.

  PMID: 36959540 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pluvicto

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Wouter V Vogel, MD, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter prospective phase I study investigating standard of care treatment for node-positive prostate cancer (7 weeks EBRT and 3 years ADT) complemented with 1 or 2 concurrent cycles of systemic 177Lu-PSMA-617 delivered in week 2 (and 4) of EBRT. The tolerability of adding 177Lu-PSMA-617 will be evaluated using a Bayesian Optimal Interval (BOIN) dose-escalation design based on the occurrence of grade 3 acute toxicity.

Study Record Dates

• First Submitted: October 7, 2021
• First Posted: December 17, 2021
• Study Start: December 20, 2021
• Primary Completion: September 9, 2025
• Study Completion: September 9, 2025
• Last Updated: December 10, 2025

Record last verified: 2025-12

Locations

NL (2)