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

NCT03828838 | Completed Phase 1

• 1 other identifier: NL62774.09L.r7
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Neoplasm

Outcome Measures

Primary Outcomes (4)

• Doses delivered to the tumors

  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

  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

  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

  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 Outcomes (4)

• PSA progression free survival

  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)

  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

  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

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

Study Arms (1)

Lu-177 PSMA-617

EXPERIMENTAL

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

Drug: Lu-177 PSMA-617

Interventions

Lu-177 PSMA-617 DRUG

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

Also known as: Lutetium-177 Prostate Specific Membrane Antigen

Lu-177 PSMA-617

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radiology and Nuclear Medicine

Nijmegen, Gelderland, 6525GA, Netherlands

Location

Related Publications (2)

• Peters SMB, Mink MCT, Prive BM, de Bakker M, de Lange F, Muselaers CHJ, Mehra N, Witjes JA, Gotthardt M, Nagarajah J, Konijnenberg MW. Optimization of the radiation dosimetry protocol in Lutetium-177-PSMA therapy: toward clinical implementation. EJNMMI Res. 2023 Jan 24;13(1):6. doi: 10.1186/s13550-023-00952-z.

  PMID: 36692682 DERIVED

• 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.

  PMID: 33883176 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

• James Nagarajah, Prof.

  Radboudumc, Nijmegen, Nederland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2019
• First Posted: February 4, 2019
• Study Start: July 1, 2018
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: November 14, 2019

Record last verified: 2019-01

Locations

NL (1)