Lu-177 Ludotadipep for Prostate Cancer
(LUCIDA Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: FutureChem
Must be taking: GnRH therapy
Must not be taking: Anticoagulants, Herbal products
Disqualifiers: Impaired organ function, Brain metastasis, Thromboembolism, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests the safety and effectiveness of a radioactive drug called [177Lu]Ludotadipep. The drug works by delivering radiation directly to certain cells to treat the condition. Lutetium-177 (177Lu) has been widely used in targeted therapy, particularly in peptide receptor radionuclide therapy (PRRT) for treating neuroendocrine tumors.
Do I need to stop my current medications for the trial?
The trial does not specify if you need to stop taking your current medications, but it does allow ongoing androgen deprivation therapy and requires stable doses of bisphosphonate therapy. You should discuss your specific medications with the trial team.
What data supports the effectiveness of the drug Lu-177 Ludotadipep for prostate cancer?
In a study with 30 patients, [177Lu]Ludotadipep showed promising results for prostate cancer, with 66.7% of patients experiencing a decrease in PSA levels, which is a marker for prostate cancer activity, and 37.5% showing a significant reduction of 50% or more. This suggests that the drug could be effective for patients who have not responded to other treatments.
12345Is Lu-177 Ludotadipep safe for use in humans?
While specific safety data for Lu-177 Ludotadipep is not available, similar treatments like [177Lu]Lu-PSMA-617 have shown a good safety profile in clinical trials for prostate cancer. Common side effects include fatigue, nausea, dry mouth, and mild bone marrow suppression, but these treatments are generally considered safe even for patients who have undergone extensive prior treatments.
26789What makes the drug Lu-177 Ludotadipep unique for treating prostate cancer?
Lu-177 Ludotadipep is a novel treatment that targets prostate-specific membrane antigen (PSMA) in prostate cancer cells, delivering radiation directly to the cancer and surrounding areas. This approach is similar to other PSMA-targeted therapies but may offer a new option for patients with limited treatment choices.
210111213Eligibility Criteria
Men aged 18+ with advanced prostate cancer that has resisted hormone therapy and progressed after treatments like enzalutamide or abiraterone. They must have PSMA positive lesions, be on stable doses of bisphosphonate if applicable, may have had taxane chemotherapy or not based on certain conditions, and should have an expected lifespan of at least 3 months for Phase 1 (6 months for Phase 2a). Participants need to use birth control during the study.Inclusion Criteria
Patients who have partners of childbearing potential must use a method of birth control
Serum testosterone level < 50 ng/dL
Able and willing to provide signed informed consent and comply with protocol requirements
+7 more
Exclusion Criteria
I have not had a blood clot in the past 3 months.
I have brain metastasis or active leptomeningeal disease.
I haven't had cancer treatment in the last 4 weeks, with some exceptions.
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
4 weeks
1 visit (in-person)
Phase 1 Treatment
Participants receive a single dose of [177Lu]Ludotadipep to determine safety and tolerability
8 weeks
Continuous monitoring for adverse events
Phase 2a Treatment
Participants receive repeated doses of [177Lu]Ludotadipep every 8 weeks to evaluate safety and efficacy
up to 40 weeks
4 to 6 visits (in-person) every 8 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 weeks after each dose
2 visits (in-person) after each dose
Long-term Follow-up
Participants are monitored every 6 months for 2 years, with an option for long-term follow-up up to 10 years
2 to 10 years
Participant Groups
[177Lu]Ludotadipep is being tested in two phases. Phase 1 aims to find the safest dose by starting with a single injection of 3.7 GBq, possibly lowering it if needed. In Phase 2a, they'll test this dose's safety and effectiveness when given repeatedly based on results from earlier trials.
1Treatment groups
Experimental Treatment
Group I: [177Lu]Ludotadipep 3.7 GBqExperimental Treatment1 Intervention
If investigators observed one or no DLT in 6 patients at the 3.7 GBq dose level, the study can advance to the Phase 2a part of the trial after the safety review committee (SRC) review.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
VA Greater Los Angeles Healthcare System,Cancer Center ResearchLos Angeles, CA
Pennsylvania Cancer Specialists & Research Institute (Formerly Gettysburg Cancer Center)Gettysburg, PA
University of MarylandBaltimore, MD
Chesapeake Urology Research AssociatesTowson, MD
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Who Is Running the Clinical Trial?
FutureChemLead Sponsor
References
A Single Dose of Novel PSMA-Targeting Radiopharmaceutical Agent [177Lu]Ludotadipep for Patients with Metastatic Castration-Resistant Prostate Cancer: Phase I Clinical Trial. [2022][177Lu]Ludotadipep, which enables targeted delivery of beta-particle radiation to prostate tumor cells, had been suggested as a promising therapeutic option for mCRPC. From November 2020 to March 2022, a total of 30 patients were enrolled for single dose of [177Lu]Ludotadipep RPT, 6 subjects in each of the 5 different activity groups of 1.9 GBq, 2.8 GBq, 3.7 GBq, 4.6 GBq, and 5.6 GBq. [177Lu]Ludotadipep was administered via venous injection, and patients were hospitalized for three days to monitor for any adverse effects. Serum PSA levels were followed up at weeks 1, 2, 3, 4, 6, 8, and 12, and PSMA PET/CT with [18F]Florastamin was obtained at baseline and again at weeks 4 and 8. The subjects required positive PSMA PET/CT prior to [177Lu]Ludotadipep administration. Among the 29 subjects who received [177Lu]Ludotadipep, 36 treatment emergent adverse events (TEAEs) occurred in 17 subjects (58.6%) and 4 adverse drug reactions (ADRs) in 3 subjects (10.3%). Of the total 24 subjects who had full 12-week follow-up data, 16 (66.7%) showed decrease in PSA of any magnitude, and 9 (37.5%) showed a decrease in PSA by 50% or greater. A total of 5 of the 24 patients (20.8%) showed disease progression (PSA increase of 25% or higher from the baseline) at the 12th week following single dose of [177Lu]Ludotadipep. These data thus far suggest that [177Lu]Ludotadipep could be a promising RPT agent with low toxicity in mCRPC patients who have not been responsive to conventional treatments.
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).
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.
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.
Factors predicting biochemical response and survival benefits following radioligand therapy with [177Lu]Lu-PSMA in metastatic castrate-resistant prostate cancer: a review. [2022]Label="BACKGROUND">Prostate cancer (PC) is one of the most common cancers in men. Although the overall prognosis is favorable, the management of metastatic castration-resistant prostate cancer (mCRPC) patients is challenging. Usually, mCRPC patients with progressive disease are considered for radioligand therapy (RLT) after exhaustion of other standard treatments. The prostate-specific membrane antigen (PSMA) labeled with Lutetium-177 ([177Lu]Lu-PSMA) has been widely used, showing favorable and successful results in reducing prostate-specific antigen (PSA) levels, increasing quality of life, and decreasing pain, in a multitude of studies. Nevertheless, approximately thirty percent of patients do not respond to [177Lu]Lu-PSMA RLT. Here, we only reviewed and reported the evaluated factors and their impact on survival or biochemical response to treatment to have an overview of the potentialprognostic parameters in [177Lu]Lu-PSMA RLT.
Clinical Trial Protocol for LuTectomy: A Single-arm Study of the Dosimetry, Safety, and Potential Benefit of 177Lu-PSMA-617 Prior to Prostatectomy. [2022]LuTectomy is an open-label phase 1/2 nonrandomised clinical trial evaluating the dosimetry, efficacy, and toxicity of the lutetium-177-radiolabelled small molecule PSMA-617 in men with high-risk localised/locoregional advanced prostate cancer with high prostate-specific membrane antigen expression who are undergoing radical prostatectomy and pelvic lymph node dissection.
Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. [2023]Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) based radiopharmaceuticals has emerged as a therapeutic area in the field of nuclear medicine and oncology, allowing for personalized medicine. Since the first market authorization in 2018 of [¹⁷⁷Lu]Lu-DOTATATE (Lutathera®) targeting somatostatin receptor type 2 in the treatment of gastroenteropancreatic neuroendocrine tumors, intensive research has led to transfer innovative 177Lu containing pharmaceuticals to the clinic. Recently, a second market authorization in the field was obtained for [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto®) in the treatment of prostate cancer. The efficacy of 177Lu radiopharmaceuticals are now quite well-reported and data on the safety and management of patients are needed. This review will focus on several clinically tested and reported tailored approaches to enhance the risk-benefit trade-off of radioligand therapy. The aim is to help clinicians and nuclear medicine staff set up safe and optimized procedures using the approved 177Lu based radiopharmaceuticals.
Lutetium-177-PSMA-617: A Vision of the Future. [2022]In the last decade, many life-prolonging therapeutic options have emerged for metastatic castration-resistant prostate cancer (mCRPC). The recent VISION trial is the first to demonstrate a survival benefit of Lutetium-177[177Lu]Lu-PSMA-617 in post-chemotherapy mCRPC. This journal club reviews the VISION trial in the context of the earlier TheraP trial of [177Lu]Lu-PSMA-617 in mCRPC post docetaxel and androgen pathway inhibition, to provide direction for the real-world application of [177Lu]Lu-PSMA-617. Treatment in the control groups differed significantly between both trials and may have influenced outcomes: TheraP mandated cabazitaxel whereas VISION's design could not allow it. In both trials, [177Lu]Lu-PSMA-617 had a good safety profile, with common adverse events being fatigue, nausea, dry mouth, marrow suppression and diarrhea. Given its efficacy and favorable safety even in heavily pre-treated patients, [177Lu]Lu-PSMA-617 provides hope to mCRPC patients and may be applied to earlier disease stages in future investigations.
EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands. [2022]The purpose of the EANM Dosimetry Committee is to provide recommendations and guidance to scientists and clinicians on patient-specific dosimetry. Radiopharmaceuticals labelled with lutetium-177 (177Lu) are increasingly used for therapeutic applications, in particular for the treatment of metastatic neuroendocrine tumours using ligands for somatostatin receptors and prostate adenocarcinoma with small-molecule PSMA-targeting ligands. This paper provides an overview of reported dosimetry data for these therapies and summarises current knowledge about radiation-induced side effects on normal tissues and dose-effect relationships for tumours. Dosimetry methods and data are summarised for kidneys, bone marrow, salivary glands, lacrimal glands, pituitary glands, tumours, and the skin in case of radiopharmaceutical extravasation. Where applicable, taking into account the present status of the field and recent evidence in the literature, guidance is provided. The purpose of these recommendations is to encourage the practice of patient-specific dosimetry in therapy with 177Lu-labelled compounds. The proposed methods should be within the scope of centres offering therapy with 177Lu-labelled ligands for somatostatin receptors or small-molecule PSMA.
Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. [2023]Label="BACKGROUND">Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 (177Lu)-PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment.
Evaluation of PSMA target diagnostic PET tracers for therapeutic monitoring of [177Lu]ludotadipep of prostate cancer: Screening of PSMA target efficiency and biodistribution using [18F]DCFPyL and [68Ga]PSMA-11. [2023]We have compared the similarity of the in vivo distribution of the prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging agents [18F]DCFPyL, [68Ga]galdotadipep, and [68Ga]PSMA-11. This study is designed for a further selection of a PSMA-targeted PET imaging agent for the therapeutic evaluation of [177Lu]ludotadipep, our previously developed prostate-specific membrane antigen (PSMA)-targeted prostate cancer therapeutic radiopharmaceutical. In vitro cell uptake was performed to evaluate the affinity to PSMA using PSMA + PC3-PIP, and PSMA- PC3-flu was used for the study. MicroPET/CT 60 min dynamic imaging and biodistribution were performed at 1, 2, and 4 h after injection. Autoradiography and immunohistochemistry were performed to evaluate the PSMA + tumor target efficiency. In the microPET/CT image, [68Ga]PSMA-11 showed the highest uptake in the kidney among all three compounds. [18F]DCFPyL and [68Ga]PSMA-11 showed similar patterns of in vivo biodistribution and high tumor targeting efficiency, similar to those of[68Ga]galdotadipep. All three agents showed high uptake in tumor tissue on autoradiography, and PSMA expression was confirmed by immunohistochemistry. Thus, [18F]DCFPyL or [68Ga]PSMA-11 can be used as a PET imaging agent to monitor [177Lu]ludotadipep therapy in prostate cancer patients.
[Lutetium-177-PSMA in metastasized prostate carcinoma]. [2023]Lutetium-177 coupled with a ligand for Prostate Specific Membrane Antigen ([177Lu]Lu-PSMA) is a new treatment in The Netherlands. Patients with metastasized castration resistant prostate carcinoma and progressive disease after hormonal therapy and chemotherapy, and no other regular therapeutic options, can be referred. A good clinical performance state, adequate bone marrow function and a PSMA PET/CT showing adequate targeting in all metastases are essential. The therapy consists of four to six intravenous administrations of 7.4 GBq [177Lu]Lu-PSMA, six weeks apart. Side effects are mild and consist of xerostomia, fatigue and bone marrow depression. This therapy is currently administered only in a few hospitals in The Netherlands, mainly in research setting. An EMA registered product is expected at the end of 2022, which can contribute to better availability for reimbursed treatment.
[Lutetium-177-PSMA in metastasized prostate carcinoma]. [2023]Lutetium-177 coupled with a ligand for Prostate Specific Membrane Antigen ([177Lu]Lu-PSMA) is a new treatment in The Netherlands. Patients with metastasized castration resistant prostate carcinoma and progressive disease after hormonal therapy and chemotherapy, and no other regular therapeutic options, can be referred. A good clinical performance state, adequate bone marrow function and a PSMA PET/CT showing adequate targeting in all metastases are essential. The therapy consists of four to six intravenous administrations of 7.4 GBq [177Lu]Lu-PSMA, six weeks apart. Side effects are mild and consist of xerostomia, fatigue and bone marrow depression. This therapy is currently administered only in a few hospitals in The Netherlands, mainly in research setting. An EMA registered product is expected at the end of 2022, which can contribute to better availability for reimbursed treatment.