This is a non-randomized, open-label phase II study designed to estimate 12-month treatment-free survival rate following total consolidative metastasis-and-primary directed therapy (MPDT) among patients with partial response/stable disease after at least 6 months of immune checkpoint blockade-based therapy for metastatic clear cell RCC. The investigators hypothesize that patients who undergo total consolidative MPDT followed by systemic therapy discontinuation will have a 12-month treatment-free survival rate of 32% compared to a null hypothesis of 13%
Histologically or cytologically confirmed diagnosis of clear cell renal cell carcinoma (mixed histology acceptable but must have clear cell component)
Metastatic clear cell RCC with 5 or fewer metastases at enrollment (excluding pulmonary nodules <1.0cm)
Stable disease or partial response as assessed by investigators following at least 6 months of immune checkpoint blockade-based therapy.
Has disease amenable for total consolidative focal therapy (this will be determined by a multidisciplinary team which may include a combination of medical oncologists, urologists, interventional radiologists, and radiation oncologists).
Subjects who have progressed during the first 6 months of immune checkpoint-blockade based therapy as determined by study investigator.
Subjects who have a need for urgent focally directed therapy (i.e. symptomatic brain or spinal metastases). Stable spinal metastases resected and/or treated with SBRT in advance of or concurrently with immune checkpoint-blockade based therapy are allowed to participate.
Any female of child-bearing potential who has a positive urine pregnancy test within 72 hours before screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Participants must be excluded/discontinued from the trial in the event of a positive or borderline positive serum pregnancy test result.
Single group
Total consolidative MPDT
Procedure/SurgeryAfter stopping systemic anti-cancer therapy for metastatic RCC, participant will receive one or more of the following: surgery (e.g. nephrectomy, metastasectomy, lymph node dissection), percutaneous cryoablation and/or radiotherapy (SAbR or other definitive radiotherapy).
Treatment-free survival
Treatment-free survival, defined as the time from discontinuation of anti-cancer therapy until either: 1) the resumption of systemic therapy; 2) the first date of additional focally-directed therapy; or 3) death.
Recurrence-free survival
Recurrence-free survival, defined as the time from completion of total consolidative MPDT until investigator-assessed disease recurrence.
Grade 3 or higher adverse events
Grade 3 or higher adverse events according to the Clavien-Dindo scale (surgery), Society for Interventional Radiology scale (percutaneous cryoablation), or the CTCAE v5.0 (radiotherapy)
Identify an immune signature that correlates with treatment free survival
The investigators will broadly interrogate immune cell types from the peripheral blood and tumor tissue
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