Lutetium-177-PSMA-617 in Low Volume Metastatic Prostate Cancer

November 13, 2019 updated by: Radboud University Medical Center

Pilot Study: Lutetium-177-PSMA-617 in Low Volume Metastatic Prostate Cancer

Radioligand therapy (RLT) using Lu-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 (mCRPC) patients. However, there are no prospective studies published so far using this treatment approach in hormone sensitive setting. In this pilot study patients with hormone sensitive prostate cancer who did not undergo hormonal treatment will be treated with Lu-177 PSMA-617.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Radioligand therapy (RLT) 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 in nuclear medicine departments world-wide 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 PSMA ligand PSMA-617 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%. These results were confirmed in a smaller scale prospective study published recently.

Although these results are very promising, it is noteworthy that all currently Lu-177-PSMA-617 RLT only has been evaluated in end stage prostate cancer patients to date. In theory, RLT could be more effective in low volume disease because of the very high tumor uptake of radioligands in small lesions. There are no published data so far evaluating the therapeutic effect of Lu-177-PSMA-617 RLT in an earlier stage of the disease. Because of the difference in tumor load between mCRPC patients and patients with low volume metastatic disease, dosimetry and toxicity in these patients need evaluation. Here a clinical trial to investigate the efficacy of Lu-177-PSMA-617 RLT in patients with low volume metastatic prostate cancer, prior to the hormone insensitive state is proposed.

Objective: The aim of this study is to evaluate the dosimetry and toxicity of Lu-177-PSMA-617 RLT, in patients with low volume, hormone sensitive metastatic prostate cancer under treatment condition. Ultimately, the goal of this study is to stabilize previously progressive disease in these patients and to improve the quality of life by postponing the need for androgen deprivation therapy (ADT).

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6525GA
        • Radiology and Nuclear Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Histological proven adenocarcinoma of the prostate
  • Prior local therapy for prostate cancer
  • Biochemical recurrence or clinical progression after local therapy (PSA > 0.2 µg/l),
  • PSA-DT < 6 months
  • Gallium-68 (68Ga)-PSMA-PET-CT positive metastases in bones and/or lymph nodes (N1/M1ab): ≥1, maximally 10 metastases (at least 1 lesion with a lesion size of ≥1 cm to enable adequate dosimetry studies)
  • 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)
  • No prior hormonal therapy or chemotherapy; testosteron > 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 3 months
  • No visceral metastases

  • Laboratory values:

    • White blood cells > 3.5 x 109/l
    • Platelet count > 150 x 109/l
    • Hemoglobin > 6 mmol/l
    • Alanine transaminase, aspartate aminotransferase < 3 x upper limit of normal
    • Modification of Diet in Renal Disease Study glomerular filtration rate ≥ 60 ml/min
  • Signed informed consent

Exclusion Criteria:

  • No detectable lesions on the Ga-68 PSMA PET/CT with an uptake level below the liver uptake.
  • A known subtype other than prostate adenocarcinoma
  • 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 and nano Magnet Resonance Tomography (nMRI)
  • Contra-indication for MRI imaging (claustrophobia, implanted electric and electronic devices (heart pacemakers, insulin pumps, implanted hearing aids, neurostimulators), intracranial metal clips, metallic bodies in the eye)
  • Contra-indication for Buscopan (allergy to hyoscine or any other ingredients of this medication, allergy to to other atropines (e.g. atropine, scopolamine), myasthenia gravis, enlarged colon, glaucoma or obstructive prostatic hypertrophy)
  • Additional contra-indications for the intravenous injection form of Buscopan (taking blood thinning medication (e.g. warfarin, heparin), narrowing of the gastrointestinal tract, fast heartbeat, angina or heart failure)
  • Contra-indication to glucagon (pheochromocytoma)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lu-177 PSMA-617
Two cycles with 3 and 3-6 GBq Lu-177 PSMA-617 (including 3D-dosimetry)
Drug: Lu-177 PSMA-617
Two cycles of Lu-177 PSMA (3GBq and 3-6 GBq)
Other Names:
  • Lutetium-177 Prostate Specific Membrane Antigen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Doses delivered to the tumors
Time Frame: For cycle 1 (duration of one cycle is 56 days)
Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to the tumors
For cycle 1 (duration of one cycle is 56 days)
Doses delivered to the tumors
Time Frame: For cycle 2 (duration of one cycle is 56 days)
Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to the tumors
For cycle 2 (duration of one cycle is 56 days)
Doses delivered to organs at risk
Time Frame: For cycle 1 (duration of one cycle is 56 days)
Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to all organs at risk
For cycle 1 (duration of one cycle is 56 days)
Doses delivered to organs at risk
Time Frame: For cycle 2 (duration of one cycle is 56 days)
Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to all organs at risk
For cycle 2 (duration of one cycle is 56 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PSA progression free survival
Time Frame: Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle
PSA progression free survival, defined as the time from baseline to PSA progression, assessed using PCWG3 criteria on blood test results.
Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle
Uptake on prostate specific membrane antigen (PSMA) positron emission tomography (PET)
Time Frame: Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle
Comparing the changes on baseline PSMA PET and after each cycle (defined according to EORTC PET response criteria)
Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle
Radiographic progression free survival
Time Frame: Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle
Radiographic progression free survival - defined as the time from baseline to radiographic progression (assessed using Prostate Cancer Working Group 3 (PCWG3) criteria for bone lesions and RECIST 1.1 for soft tissue lesions)
Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle
Health-related quality of life
Time Frame: Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle
Health-related quality of life, assessed using a composite of the European Organisation of Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ C-30)
Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Investigators

  • Principal Investigator: James Nagarajah, Prof., Radboudumc, Nijmegen, Nederland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2018

Primary Completion (Actual)

November 1, 2019

Study Completion (Actual)

November 1, 2019

Study Registration Dates

First Submitted

January 9, 2019

First Submitted That Met QC Criteria

February 1, 2019

First Posted (Actual)

February 4, 2019

Study Record Updates

Last Update Posted (Actual)

November 14, 2019

Last Update Submitted That Met QC Criteria

November 13, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL62774.09L.r7

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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