Radiopharmaceutical treatment for advanced kidney cancer using 177Lu-PSMA-617

Inclusion Criteria:

PRE-SCREENING

* Histologically proven ccRCC. Sarcomatoid component is allowed.
* Adult patients ≥18 years old.
* Has progressed on or after ≥1-line prior systemic therapy approved in the metastatic setting. Prior treatment must include an anti-programmed death-1 (receptor) \[PD-1\]/programmed death-ligand 1 (PD-L1) therapy +/- ipilimumab and a VEGFR-TKI.
* Written pre-screening informed consent according to ICH/GCP and local regulations.

SCREENING

* Patients with at least one PSMA-positive metastatic lesion, and no exclusionary PSMA-negative lesions, with positive lesions defined as those with a maximum standardized uptake value (SUVmax) greater than the mean standardized uptake value (SUVmean) of liver background.
* Measurable disease by RECIST 1.1 criteria.
* Patients with adequate blood tests (Absolute neutrophil count \> 1.5 x 109/L, haemoglobin \> 9.0 g/dL, platelet count \> 100,000/µL, estimated glomerular filtration rate (GFR) ≥ 40 ml/min by CKD-EPI formula, total bilirubin ≤ 1.5 x ULN. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastases).
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Women of childbearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to registration. A positive urine pregnancy test result must immediately be confirmed using a serum test. A pregnancy test is to be reported within 7 days prior to the first dose of the study treatment.

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:

  * Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
  * Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
  * Intrauterine device (IUD)
  * Intrauterine hormone-releasing system (IUS)
  * Bilateral tubal occlusion
  * Vasectomized partner
  * Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
  * Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 3 months after the last study treatment.
* Before patient's enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations. This includes consent to comply to recommended radioprotection precautions during study.

Exclusion Criteria:

* Patient with RCC in a single kidney.
* Patients with PSMA-negative lesions (defined as PSMA uptake equal to or lower than that of liver parenchyma) in any lymph node with a short axis of at least 15 mm, in any metastatic solid-organ lesions with a short axis of at least 1.0 cm, or in any metastatic bone lesion with a soft-tissue component of at least 1.0 cm in the short axis. Patients with any PSMA-negative metastatic lesion meeting these criteria are ineligible.
* Other malignancy that is expected to interfere with the treatment or results of this study, such as prostate cancer.
* Patient with active uncontrolled or symptomatic central nervous system (CNS metastases).

Note: patients treated previously with radiotherapy and/or surgery resulting in controlled/asymptomatic CNS disease are allowed.

* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the in the trial.
* Known contraindication to imaging tracer or any product of contrast media.