Consolidative Metastasis and Primary Directed Therapy (MPDT) for Renal Cell Carcinoma (RCC)

A Phase II Study of Total Consolidative Metastasis-and-primary Directed Therapy (MPDT) for Renal Cell Carcinoma (RCC).

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%

Inclusion Criteria:

• 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).
• ECOG performance status < 2
• Must have archival tissue (slide or Formalin-Fixed Paraffin-Embedded tissue) preceding prior systemic treatment for comparison to tissue from consolidation
• Consolidation surgery and biopsies are strongly encouraged to be within 42 days +/- 7 days of holding systemic therapy.

Exclusion Criteria:

• 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.