- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05162573
EBRT + Lu-PSMA for N1M0 Prostate Cancer (PROQURE-1)
Tolerability of Concurrent EBRT + Lu-PSMA for Node-positive Prostate Cancer (PROQURE-1)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Rationale: In the past, prostate cancer patients with nodal metastases (clinically N1M0) were not considered for curative treatment, based on the hypothesis that these patients are affected by systemic disease. Today, patients with primary diagnosed N1M0 prostate cancer increasingly receive curative intent high-dose external beam radiotherapy (EBRT) to the prostate and regional nodes combined with up to 3 years androgen deprivation therapy (ADT). This aggressive and lengthy multimodal treatment can achieve long-term disease-free and overall survival, but it also comes with significant toxicity and failure rates of up to 47% within 5 years with locoregional recurrence within radiotherapy fields and/or distant progression. A new strategy is needed to (1) enhance EBRT to better control macroscopic tumor in the prostate and involved nodes, (2) better treat undetected microscopic disease inside and outside EBRT fields, and (3) potentially reduce or obviate the long use of ADT with its toxicity and associated poor quality of life. Radioligand therapy (RLT) with Lutetium-177 labeled PSMA-ligands (177Lu-PSMA-617) can selectively deliver radiation dose to both macroscopic and microscopic tumor locations throughout the body, with limited systemic toxicity. Based on radiobiologic considerations, the hypothesis is that complementing EBRT with concurrent 177Lu-PSMA-617 can provide synergistic anti-tumor effects, without prolonging overall treatment time and with limited toxicity. The feasibility of this innovative use of "RLT as the ultimate radiosensitizer for EBRT" now needs to be explored.
Objective: Primary: To determine the maximum tolerated dose (MTD) of 1 or 2 cycles 177Lu-PSMA-617 when given concurrent with EBRT+ADT. Secondary: To demonstrate acceptable late toxicity at 6 months, superior dosimetric efficacy, anti-tumor efficacy at 6 months, feasibility of QoL evaluation and favorable pharmacokinetics.
Study design: Multicenter prospective phase I dose-escalation study, using a BOIN design, with 4 dose levels for 177Lu-PSMA-617 and a maximum of 24 patients.
Study population: Patients with primary diagnosed prostate cancer, clinical stage T2-T4N1M0 based on MRI and PSMA PET/CT, with a PSMA-positive index tumor within the prostate and involved nodes all within EBRT fields (highest node below the level of the aortic bifurcation).
Intervention: Standard of care treatment (EBRT of prostate and pelvic nodes with concurrent ADT) is complemented with 1 or 2 concurrent cycles dose-escalated 177Lu-PSMA-617 in week 2 (and 4).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participation in the study involves one day hospitalization per administration with IV catheter and administration of 3, 6 or 9 or 2x7.4 GBq 177Lu-PSMA-617 in week 2 (and week 4) of EBRT, and during the week after each administration 3 SPECT/CT scans from pelvis to head for dosimetry and 11 blood samples for pharmacokinetics. Patient receives additional radiation exposure from 177Lu-PSMA-617, which comes with a low risk for acute toxicity (infusion reaction, nausea, vomiting), low risk for late toxicity (temporary salivary gland function loss), a maximum of one of two days hospitalization in isolation, and after discharge about 2 weeks radiation safety measures at home. These disadvantages are considered acceptable for patients with node-positive prostate cancer, in the scope of potential improvements in tumor control with associated benefits in survival and QoL, for included patients as well as for future patients.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Wouter V Vogel, MD, PhD
- Phone Number: +31205129111
- Email: w.vogel@nki.nl
Study Locations
-
-
-
Amsterdam, Netherlands, 1066 CX
- Recruiting
- Netherlands Cancer Institute
-
Contact:
- Wouter V Vogel, MD, PhD
- Phone Number: +31205129111
- Email: w.vogel@nki.nl
-
Utrecht, Netherlands, 3508 GA
- Recruiting
- UMC Utrecht
-
Contact:
- Arthur JA Braat, MD, PhD
- Email: a.j.a.t.braat@umcutrecht.nl
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: EBRT + 3 GBq Lu-PSMA
|
External Beam Radiotherapy
Dose-escalation of 177Lu-PSMA-617 (3, 6, 9 or 2x7.4 GBq) combined with external beam radiotherapy (EBRT)
|
Experimental: EBRT + 6 GBq Lu-PSMA
|
External Beam Radiotherapy
Dose-escalation of 177Lu-PSMA-617 (3, 6, 9 or 2x7.4 GBq) combined with external beam radiotherapy (EBRT)
|
Experimental: EBRT + 9 GBq Lu-PSMA
|
External Beam Radiotherapy
Dose-escalation of 177Lu-PSMA-617 (3, 6, 9 or 2x7.4 GBq) combined with external beam radiotherapy (EBRT)
|
Experimental: EBRT + 2x7.4 GBq Lu-PSMA
|
External Beam Radiotherapy
Dose-escalation of 177Lu-PSMA-617 (3, 6, 9 or 2x7.4 GBq) combined with external beam radiotherapy (EBRT)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose (MTD)
Time Frame: from start of EBRT until 3 months after EBRT
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose-limiting-toxicity (DLT)
Time Frame: From start of EBRT until 3 months after EBRT
|
grade 3 toxicity according to CTCAE v5.0
|
From start of EBRT until 3 months after EBRT
|
Late toxicity
Time Frame: 6 months after EBRT
|
grade 3 toxicity according to CTCAE v5.0
|
6 months after EBRT
|
Anti-tumor efficacy
Time Frame: 6 months after EBRT
|
PSA response
|
6 months after EBRT
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Wouter V Vogel, MD, PhD, The Netherlands Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- M21PQ1
- 2020-005577-27 (EudraCT Number)
- NL75976.031.21 (Other Identifier: Centrale Commissie Mensgebonden Onderzoek (CCMO))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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