European Organisation for Research and Treatment of Cancer - EORTC
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: * Be diagnosed with advanced kidney cancer previously treated with immunotherapy and targeted therapy. * Test positive for PSMA on a PET scan. * Be generally healthy and able to perform daily activities. * Be at least 18 years of age. 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.
Metastatic Clear Cell Renal Cell Carcinoma
177Lu-PSMA-617
PHASE2
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: * To assess the safety profile of 177Lu -PSMA-617 in patients with metastatic ccRCC * To estimate disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) of participants with metastatic ccRCC treated with 177Lu-PSMA-617 * To estimate the time to start subsequent systemic treatment for patients with metastatic ccRCC treated with 177Lu-PSMA-617. 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.
| Study Type : | INTERVENTIONAL |
| Estimated Enrollment : | 48 participants |
| Masking : | NONE |
| Primary Purpose : | TREATMENT |
| Official Title : | Phase II Trial Evaluating the Efficacy of 177Lutetium-PSMA-617 Treatment in Patients With Metastatic Clear Cell Renal Carcinoma Cell With Progressive Disease on First-line or Second-line Systemic Treatment |
| Actual Study Start Date : | 2025-10-30 |
| Estimated Primary Completion Date : | 2028-01-30 |
| Estimated Study Completion Date : | 2029-01-01 |
Information not available for Arms and Intervention/treatment
| Ages Eligible for Study: | 18 Years to 100 Years |
| Sexes Eligible for Study: | ALL |
| Accepts Healthy Volunteers: |
Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.
No Location Found