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

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ClinicalTrials.gov Identifier: NCT03828838
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : February 4, 2019
Sponsor:
Information provided by (Responsible Party):
Radboud University

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.

Condition or disease Intervention/treatment Phase
Prostate Neoplasm Drug: Lu-177 PSMA-617 Phase 1 Phase 2

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).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study: Lutetium-177-PSMA-617 in Low Volume Metastatic Prostate Cancer
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Lutetium

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 Name: Lutetium-177 Prostate Specific Membrane Antigen




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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


Secondary Outcome Measures :
  1. 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.

  2. 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)

  3. 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)

  4. 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)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03828838


Contacts
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Contact: Basiaan Privé, MD +31 (0)24 3090031 bastiaan.prive@radboudumc.nl

Locations
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Netherlands
Radiology and Nuclear Medicine Recruiting
Nijmegen, Gelderland, Netherlands, 6525GA
Contact: Bastiaan Privé, MD    +31 (0)24 3090031    bastiaan.prive@radboudumc.nl   
Sponsors and Collaborators
Radboud University
Investigators
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Principal Investigator: James Nagarajah, Prof. Radboudumc, Nijmegen, Nederland

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Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT03828838     History of Changes
Other Study ID Numbers: NL62774.09L.r7
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases