A Phase 2 interventional study of 177Lu-PSMA-617 in Metastatic Clear Cell Renal Cell Carcinoma, sponsored by European Organisation for Research and Treatment of Cancer - EORTC. Recruiting at 2 sites in France. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-06-04.
Sponsored by European Organisation for Research and Treatment of Cancer - EORTC · Phase 2, Interventional, and Treatment
Background This study is for adults with advanced kidney cancer that has spread to other parts of the body and has continued to progress despite treatment with immunotherapy and targeted therapy. Unfortunately, treatment options at this stage of the disease are limited. The existing treatments' ability to work against cancer has not been fully looked into.
Rationale The goal of this study is to examine if a new drug treatment called 177Lutetium-PSMA-617, hereafter referred as 177Lu-PSMA-617, which holds the active ingredient 177Lutetium-PSMA and has been used as a standard treatment for advanced prostate cancer since December 2022, can also help treat advanced kidney cancer.
The drug 177Lu-PSMA-617 is being tested as an experimental treatment that targets a specific protein on cancer cells. This protein, known as prostate-specific membrane antigen (PSMA), is present on the surface of kidney cancer cells. Therefore, before the treatment begins, participants will undergo a PET (positron-emission tomography) scan to check if their kidney cancer cells express high levels of PSMA. This scan uses a small amount of radioactive material (in the form of 177Lutetium) to visualize the presence of PSMA on the cancer cells. Only participants who test positive for PSMA can take part in the study. In this approach, PSMA serves two purposes. First, it helps assess whether the cancer expresses this protein and allows 177Lu-PSMA-617 to specifically target and attach to the cancer cells. Second, 177Lu-PSMA-617 delivers a small amount of radiation directly to the tumour, which helps kill cancer cells while minimizing damage to normal cells. This type of treatment is known as a radiopharmaceutical.
Objective The primary aims are to find out if 177Lu-PSMA-617 is useful against kidney cancer and to assess its safety. Throughout the study, participants will undergo several imaging assessments to check their disease and response to treatment.
The study also includes the collection of tissue samples. Together with the information collected from the imaging assessments, this will allow further research into markers that may lead to earlier detection of tumour spread or help identify individuals who may benefit more from treatment with 177Lu-PSMA-617.
Treatment All participants will receive 177Lu-PSMA-617 through an intravenous injection at a standard dose of 7,400 MBq (megabecquerel: a measure of radioactivity). Treatments will be administered approximately every six weeks, for a maximum of six times.
Blood tests are done before and during treatment to check the participant's health and to detect any early side effects from the treatment. Different types of scans are performed before, during, and after 177Lu-PSMA-617 administration to check how well the treatment is working. After treatment ends, follow-up visits will be scheduled every six weeks during the first year. In the second year, your doctor will decide how often you need to come in for visits. These appointments are important for monitoring how the body continues to respond to the treatment. The entire study period will last approximately two years from the time of study entry.
Participants
The study will include approximately 56 participants who will be tested for PSMA expression, to obtain a minimum of 48 participants expressing PSMA entering the study. To qualify, participants must:
Benefit-risk analysis The drug 177Lu-PSMA-617 has proven to work well in treating advanced prostate cancer and could be a promising new treatment possibility for kidney cancer, although this has not yet been shown. By joining this study, participants will contribute to valuable research to better understand kidney cancer and improve treatment options for future patients. Participating in this study offers a chance to try a new treatment, which might help people with advanced kidney cancer live longer and prevent the disease from getting worse, especially for those who have limited treatment options left after immunotherapy and targeted therapy.
With all new treatments, there are possible risks and side effects associated with them. Side effects of the drug 177Lu-PSMA-617 may include feeling tired, nausea, dry mouth, loss of appetite, and changes in blood cells. While not all side effects are known yet, the study team will carefully follow participants for any side effects during and after treatment. It is important to understand that while the study is being done to provide new information, there are still some questions on the treatment's safety and how well it will work.
RATIONALE After progression on first-line Immune Checkpoint Inhibitor (ICI)-based treatment, sequencing of Vascular Endothelial Growth Factor-Receptor Tyrosine Kinase Inhibitors (VEGFR-TKIs) is standard of care as long as the patient derives clinical benefit. Cabozantinib and axitinib, if not given in first line, are good choices in second line. However, the response rate to VEGFR-TKIs in second line remains low, not exceeding 32-41%. In addition, there is no standard of care treatment after ICI- and VEGFR-TKI-based therapy. Therefore, novel therapeutic strategies must be developed.
Given the high efficacy and low toxicity of 177Lu-PSMA-617 reported in prostate cancer, and the observed Prostate-specific Membrane Antigen (PSMA) expression in ccRCC, we propose to evaluate 177Lu-PSMA-617 radioligand therapy (RLT) in metastatic ccRCC patients who progress after treatment with at least one ICI and one VEGFR-TKI given in sequence or in combination in the metastatic setting.
The trial will evaluate 4 cycles of 177Lu-PSMA-617 with 2 additional cycles in case of partial response (PR) or stable disease (SD).
OBJECTIVES The primary objective is to evaluate the activity of 177Lu-PSMA-617 through Objective Response in metastatic ccRCC patients progressing on or after treatment with one ICI, and one VEGFR-TKI, either in combination or in se¬quence.
The secondary objectives are:
The study is a prospective, multicentric, single arm phase II trial.
Number of patients:
Approximately 56 participants will be screened to achieve 48 enrolled to the study intervention and at least 43 to be evaluable for the primary endpoint.
This trial may be beneficial for patients with metastatic RCC progressing after ICI and VEGFR-TKI, for which efficacious alternative treatment options are lacking, and toxicity remains an issue.
These patients will be closely followed with conventional imaging as well as by PSMA-PET/CT, which has been suggested to be more sensitive than conventional imaging in detection of metastases. These patients will be followed in expert centers specialized in renal- and prostate cancer management by physicians experienced in managing progressive mRCC, as well as adverse events related to 177Lu-PSMA-617 treatment.
39 studies on the registry are indexed under Clear-cell metastatic renal cell carcinoma; 26 are open to participants now.
This study's planned enrollment of 48 is above the median of 37 across 35 interventional studies indexed under Clear-cell metastatic renal cell carcinoma.
Browse Clear-cell metastatic renal cell carcinoma studies →European Organisation for Research and Treatment of Cancer - EORTC is the lead sponsor of 342 studies on the registry; 23 are open to participants now.
Counted across the registry records on this site, refreshed daily.
PRE-SCREENING
SCREENING
Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrhoeic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antioestrogens, low body weight, ovarian suppression, or other reasons.
Patients of childbearing / reproductive potential should use adequate birth control measures during the study treatment period and for at least 14 weeks after the last dose of treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Such methods include:
Exclusion Criteria:
Note: patients treated previously with radiotherapy and/or surgery resulting in controlled/asymptomatic CNS disease are allowed.
177Lu-PSMA-617 will be administered by intravenous infusion or injection at an activity of 7.4 GBq every 6 weeks (±1 week) for up to a total of 6 doses, unless there is disease progression or unacceptable toxicity or until the occurrence of a withdrawal criterion. The first infusion should be administered within 3 weeks from enrolment. Patients in PR or SD after 4 cycles will receive an additional two doses.
Drug: 177Lu-PSMA-617
Administeration by intravenous infusion or injection at an activity of 7.4 GBq every 6 weeks (±1 week) for up to a total of 6 doses, unless there is disease progression or unacceptable toxicity or until the occurrence of a withdrawal criterion. The first infusion should be administered within 3 weeks from enrolment. Patients in PR or SD after 4 cycles will receive an additional two doses.
Objective Response
Objective Response, defined as a Complete Response (CR) or a Partial Response (PR) based on RECIST 1.1 criteria, on conventional imaging.
Time frame: 9 months after Last Patient In
safety (adverse events)
Safety in all treated patients using Common Terminology Criteria for Adverse Events (CTCAE) V5.0
Time frame: 42 months after First Patient In
Disease control rate (DCR) at 6-months
Disease control according to RECIST 1.1 at 6 months (defined as 24 weeks +/- 1 week) after treatment initiation.
Time frame: 6 months after treatment initiation
Progression-free survival (PFS)
Time frame: 42 months after First Patient In
Time to start of next systemic treatment
the overall time in months until the patient began the next systemic treatment
Time frame: 42 months after First Patient In
Overall survival (OS)
Time frame: 42 months after First Patient In
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Clear-cell metastatic renal cell carcinoma→
European Organisation for Research and Treatment of Cancer - EORTC