177Lu-PSMA-617 for Prostate Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Amir Iravani, MD

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Washington

Must be taking: Androgen deprivation therapy

Must not be taking: Radioligand therapy

Disqualifiers: CNS metastases, Congestive heart failure, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well 177Lu-PSMA-617 works in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that remains despite treatment (resistant). Lutetium Lu 177 (177Lu), the radioactive (tracer) component being delivered by prostate-specific membrane antigen (PSMA)-617, has physical properties that make it ideal radionuclide (imaging tests that uses a small dose tracer) for treatment of metastatic castrate-resistant prostate cancer (mCRPC). 177Lu-PSMA-617 works by binding to prostate cancer cells and inducing damage to deoxyribonucleic acid (DNA) inside prostate cancer cells. Giving 177Lu-PSMA-617 may improve treatment outcomes for patients with mCRPC.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have any systemic anti-cancer therapy or investigational agents within 30 days before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Lutetium Lu 177-PSMA-617 for prostate cancer?

Research shows that Lutetium Lu 177-PSMA-617 is effective in reducing prostate-specific antigen (PSA) levels and metastasis in patients with advanced prostate cancer, particularly those who have not responded to standard treatments. This treatment targets cancer cells specifically, which can improve patient outcomes and quality of life.

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Is 177Lu-PSMA-617 safe for humans?

177Lu-PSMA-617 has been studied for safety in patients with prostate cancer, and while it shows promise, the safety profile is still being evaluated. Some studies have focused on its use in combination with other treatments to improve outcomes.

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What makes the drug 177Lu-PSMA-617 unique for prostate cancer treatment?

177Lu-PSMA-617 is unique because it is a radiopharmaceutical that specifically targets prostate-specific membrane antigen (PSMA) on prostate cancer cells, delivering beta-minus radiation directly to the cancer cells. This targeted approach can be more effective and have fewer side effects compared to traditional chemotherapy, as it minimizes damage to healthy tissues.

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Eligibility Criteria

This trial is for patients with prostate cancer that has spread and is resistant to treatment. Participants must have a specific low level of PSMA expression, which will be determined by scans.

Inclusion Criteria

I understand and can follow all study requirements.

My PET/CT scan shows cancer that is PSMA positive without any PSMA negative spots.

White blood cell (WBC) count ≥ 2.5 x 10^9/L

Exclusion Criteria

Known hypersensitivity to the components of the study therapy or its analogs

I am not currently receiving any other cancer treatments like chemotherapy or immunotherapy.

I have had brain metastases, received treatment, and am now stable.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 177Lu-PSMA-617 intravenously over 30 minutes on specified days, with imaging and blood sample collection throughout the study

Up to 36 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments every 12 weeks

Up to 2 years

Every 12 weeks (in-person)

Participant Groups

The study tests the effectiveness of an intensified dose of 177Lu-PSMA-617 in treating metastatic castrate-resistant prostate cancer (mCRPC). It involves various imaging techniques like bone scans, CTs, PET-CTs, SPECT, MRI, and biospecimen collection.

Group I: Treatment (177Lu-PSMA-617) Experimental Treatment 8 Interventions

Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Fred Hutch/University of Washington Cancer Consortium Seattle, WA

University of California San Francisco San Francisco, CA

Olive View-University of California Los Angeles Medical Center Sylmar, CA

Who Is Running the Clinical Trial?

University of Washington Lead Sponsor

Society of Nuclear Medicine and Molecular Imaging (SNMMI) Mars Shot Research Fund Collaborator

Novartis Industry Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. [2021] Label="BACKGROUND">Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [177Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments.

2. England pubmed.ncbi.nlm.nih.gov

UpFrontPSMA: a randomized phase 2 study of sequential 177 Lu-PSMA-617 and docetaxel vs docetaxel in metastatic hormone-naïve prostate cancer (clinical trial protocol). [2021] Label="OBJECTIVE">To assess the activity and safety of sequential lutetium-177 (177 Lu)-PSMA-617 and docetaxel vs docetaxel on a background of androgen deprivation therapy (ADT) in men with de novo metastatic hormone-naïve prostate cancer (mHNPC).

3. England pubmed.ncbi.nlm.nih.gov

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). [2022] Label="OBJECTIVES">To determine the activity and safety of lutetium-177 (177 Lu)-prostate-specific membrane antigen (PSMA)-617 in men with metastatic castration-resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue.

4. United States pubmed.ncbi.nlm.nih.gov

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. [2023] This study investigates the predicting factors of the biochemical response and survival of patients with advanced metastatic prostate cancer who underwent therapy with radioligand lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA), often referred to as [177Lu]Lu-PSMA. This study is a review of the previous literature. This study included articles published in the last 10 years in the English language. According to the literature review, treatment with [177Lu]Lu-PSMA has a positive impact on prostate-specific antigen (PSA) within the first cycle and a negative impact on lymph node metastasis. There is a plausible positive impact on PSA after multiple cycles and performance status and a negative impact on visceral metastasis. In conclusion, the reviews show that treatment with [177Lu]Lu-PSMA in patients with castration-resistant prostate cancer is beneficial in reducing PSA and metastasis.

5. United States pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. [2023] Label="PURPOSE OF REVIEW">[177Lu]Lu-PSMA-617 is a radiopharmaceutical that emits beta-minus radiation and targets prostate-specific membrane antigen (PSMA)-positive prostate cancer. Despite its clinical success, there are still patients not showing sufficient response rates. This review compiles latest studies aiming at therapy improvement in [177Lu]Lu-PSMA-617-naïve and -resistant patients by alternative or combination treatments.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. [2023] Label="Background" NlmCategory="UNASSIGNED">Lutetium-177 [177Lu]-PSMA-617 is a targeted radioligand that binds to prostate-specific membrane antigen (PSMA) and delivers radiation to metastatic prostate cancer. The presence of PSMA-negative/FDG-positive metastases can preclude patients from being eligible for this treatment. Biology-guided radiotherapy (BgRT) is a treatment modality that utilises tumour PET emissions to guide external beam radiotherapy. The feasibility of combining BgRT and Lutetium-177 [177Lu]-PSMA-617 for patients with PSMA-negative/FDG-positive metastatic prostate cancer was explored.

7. United States pubmed.ncbi.nlm.nih.gov

177Lu-Prostate-specific Membrane Antigen Radioligand Therapy in Patients with Metastatic Castration-resistant Prostate Cancer. [2023] A 76-year-old man with metastatic castration-resistant prostate carcinoma progressing with antiandrogen and taxane therapy was treated with lutetium 177 prostate-specific membrane antigen (PSMA)-617 and showed marked biochemical and imaging response, with improvement in clinical status and osseous pain. A summary of nuclear medicine theranostics with emphasis on PSMA targeting agents is presented.

8. United States pubmed.ncbi.nlm.nih.gov

Clinical translation of (177)Lu-labeled PSMA-617: Initial experience in prostate cancer patients. [2021] PSMA-617 is reported to exhibit very high binding affinity towards PSMA receptors, over-expressed on prostate cancer cells and therefore, (177)Lu-labeled PSMA-617 is expected to play a pivotal role in the clinical management of patients suffering from ca prostate. The objective of the present study is to formulate the patient dose of (177)Lu-labeled PSMA-617, pre-clinical studies in animal model and clinical investigation in limited number of prostate cancer patients as well evaluating its potential for theranostic application.

9. Germany pubmed.ncbi.nlm.nih.gov

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial. [2022] Label="PURPOSE">Lutetium-177 prostate-specific membrane antigen-617 (177Lu-PSMA-617) in end-stage metastatic castration-resistant prostate cancer (mCRPC) has reported favourable outcomes. In this study, we aimed to prospectively compare the efficacy and safety of 177Lu-PSMA-617 and docetaxel in chemotherapy-naïve mCRPC patients.

10. United States pubmed.ncbi.nlm.nih.gov

Therapeutic Multidose Preparation of a Ready-to-Use 177Lu-PSMA-617 Using Carrier Added Lutetium-177 in a Hospital Radiopharmacy and Its Clinical Efficacy. [2022] Introduction: [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 has emerged as a promising radiopharmaceutical for targeting PSMA in metastatic castrate-resistant prostate carcinoma (mCRPC). We have optimized the radiolabeling protocol for a multidose formulation (27-28.8 GBq equivalent to 6-7 patient-doses) of [177Lu]Lu-PSMA-617 using [177Lu]Lu3+ produced via 176Lu(n,γ)177Lu route with moderate specific activity (0.66-0.81 GBq/μg). Methods: [177Lu]Lu-PSMA-617 was synthesized using moderate specific activity [177Lu]LuCl3 (0.74 GBq/μg) with PSMA-617 having metal-to-ligand molar ratio ∼1: 2.5 in CH3COONH4 buffer (0.1 M) containing gentisic acid at pH 4.0-4.5. Human prostate carcinoma cell line LNCaP cell (high PSMA expression) was used for in vitro cell-binding studies and generating tumor xenograft models in nude mice for tissue biodistribution studies. Several batches of the present formulation have been clinically administered in mCRPC patients (single patient dose: 4.44-5.55 GBq per cycle). Results: In this study we report a consistent and reproducible protocol for multidose formulations of [177Lu]Lu-PSMA-617 for adopting in a hospital radiopharmacy setting. Although the radiochemical yield of [177Lu]Lu-PSMA-617 was found to be 97.30% ± 1.03%, the radiochemical purity was 98.24% ± 0.50% (n = 19). In vitro and serum stability of [177Lu]Lu-PSMA-617 was retained up to 72 and 120 h after radiolabeling and upon storage at -20°C with a radioactive concentration between 0.37 and 0.74 GBq/mL upon using stabilizer concentration as low as 43-48 μg/mCi. Preclinical cell-binding studies of [177Lu]Lu-PSMA-617 revealed specific binding with LNCaP cells of 17.4% ± 2.4%. The uptake in LnCaP xenografted tumor (nude mice) was 7.5 ± 2.6% ID/g for ∼1.5-2.0 cm3 tumor volume at 24-h post-injection. Post-therapy (24 h) SPECT image of mCRPC patients with prior orchidectomy and various hormone therapy showed specific localization of [177Lu]Lu-PSMA-617 in the tumor region. Conclusions: Formulation of a ready-to-use multidose formulation of [177Lu]Lu-PSMA-617 was successfully achieved and the procedure was optimized for routine preparation at a hospital radiopharmacy set-up. High degree of localization of [177Lu]Lu-PSMA-617 in post-therapy SPECT scan and the post-therapeutic response confirms its therapeutic efficacy. Clinical Trials.gov ID: RPC/51/Minutes/Final dated 16th October, 2019.

11. United States pubmed.ncbi.nlm.nih.gov

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. [2022] 177Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177Lu-PSMA-617 in a large cohort of patients.