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

Primary Purpose

Prostate Neoplasm

Status

Completed

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

Lu-177 PSMA-617

About this trial

This is an interventional treatment trial for Prostate Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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)

Sites / Locations

Radiology and Nuclear Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lu-177 PSMA-617

Arm Description

Two cycles with 3 and 3-6 GBq Lu-177 PSMA-617 (including 3D-dosimetry)

Outcomes

Primary Outcome Measures

Doses delivered to the tumors

Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to the tumors

Doses delivered to the tumors

Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to the tumors

Doses delivered to organs at risk

Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to all organs at risk

Doses delivered to organs at risk

Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to all organs at risk

Secondary Outcome Measures

PSA progression free survival

PSA progression free survival, defined as the time from baseline to PSA progression, assessed using PCWG3 criteria on blood test results.

Uptake on prostate specific membrane antigen (PSMA) positron emission tomography (PET)

Comparing the changes on baseline PSMA PET and after each cycle (defined according to EORTC PET response criteria)

Radiographic progression free survival

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)

Health-related quality of life

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)

Full Information

NCT ID

NCT03828838

First Posted

January 9, 2019

Last Updated

November 13, 2019

Sponsor

Radboud University Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03828838

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

July 1, 2018 (Actual)

Primary Completion Date

November 1, 2019 (Actual)

Study Completion Date

November 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Radboud University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Neoplasm

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lu-177 PSMA-617

Arm Type

Experimental

Arm Description

Two cycles with 3 and 3-6 GBq Lu-177 PSMA-617 (including 3D-dosimetry)

Intervention Type

Drug

Intervention Name(s)

Lu-177 PSMA-617

Other Intervention Name(s)

Lutetium-177 Prostate Specific Membrane Antigen

Intervention Description

Two cycles of Lu-177 PSMA (3GBq and 3-6 GBq)

Primary Outcome Measure Information:

Title

Doses delivered to the tumors

Description

Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to the tumors

Time Frame

For cycle 1 (duration of one cycle is 56 days)

Title

Doses delivered to the tumors

Description

Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to the tumors

Time Frame

For cycle 2 (duration of one cycle is 56 days)

Title

Doses delivered to organs at risk

Description

Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to all organs at risk

Time Frame

For cycle 1 (duration of one cycle is 56 days)

Title

Doses delivered to organs at risk

Description

Calculation of the doses given in Gray per gigabequerel (Gy/GBq) delivered to all organs at risk

Time Frame

For cycle 2 (duration of one cycle is 56 days)

Secondary Outcome Measure Information:

Title

PSA progression free survival

Description

PSA progression free survival, defined as the time from baseline to PSA progression, assessed using PCWG3 criteria on blood test results.

Time Frame

Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle

Title

Uptake on prostate specific membrane antigen (PSMA) positron emission tomography (PET)

Description

Comparing the changes on baseline PSMA PET and after each cycle (defined according to EORTC PET response criteria)

Time Frame

Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle

Title

Radiographic progression free survival

Description

Time Frame

Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle

Title

Health-related quality of life

Description

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)

Time Frame

Baseline, at the end of cycle 1 and 2 (each cycle is 28 days) and 3 and 6 months after last cycle

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

James Nagarajah, Prof.

Organizational Affiliation

Radboudumc, Nijmegen, Nederland

Official's Role

Principal Investigator

Facility Information:

Facility Name

Radiology and Nuclear Medicine

City

Nijmegen

State/Province

Gelderland

ZIP/Postal Code

6525GA

Country

Netherlands

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

33883176

Citation

Prive BM, Peters SMB, Muselaers CHJ, van Oort IM, Janssen MJR, Sedelaar JPM, Konijnenberg MW, Zamecnik P, Uijen MJM, Schilham MGM, Eek A, Scheenen TWJ, Verzijlbergen JF, Gerritsen WR, Mehra N, Kerkmeijer LGW, Smeenk RJ, Somford DM, van Basten JA, Heskamp S, Barentsz JO, Gotthardt M, Witjes JA, Nagarajah J. Lutetium-177-PSMA-617 in Low-Volume Hormone-Sensitive Metastatic Prostate Cancer: A Prospective Pilot Study. Clin Cancer Res. 2021 Jul 1;27(13):3595-3601. doi: 10.1158/1078-0432.CCR-20-4298. Epub 2021 Apr 21.

Results Reference

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

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