NCT03189186

Phase-I Trial of Pembrolizumab and Percutaneous Cryoablation Combination Followed by Nephron-Sparing Surgery or Cytoreductive Nephrectomy in Locally Advanced and Metastatic Renal Cell Carcinomas

Followed by Nephron-Sparing Surgery or Cytoreductive Nephrectomy in Locally Advanced and Metastatic Renal Cell Carcinomas

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of California, Irvine · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

Patients will undergo a screening process as per standard of care to identify disease type and severity. Careful history and physical examination will also take place to rule out major heart, lung, or kidney disease and pregnancy that may affect how they will respond to the treatment. Patients with advanced (stage II and above with multiple tumors or tumors within vessels) and metastatic Renal Cell Carcinoma will be first treated with cryoablation on a large primary tumor and then given 200 mg pembrolizumab every 3-weeks 3 cycles , followed by partial/radical nephrectomy. Pembrolizumab is a biologic drug that adheres to the cell death receptors on white blood cells preventing there death and leading to an increased immunologic response. Cryoablation will be used in these patients to initially trigger and immune response to cancerous cells that is then magnified by the drug. After the surgery, patients will resume pembrolizumab for additional 5 cycles or up to a total of 2 years if a partial response is observed at the discretion of the treating medical oncologist or urologist until complete tumor remission, disease progression, unacceptable toxicity, patient refusal, or patient death due to any cause.

Detailed description

Baseline procedures: Each patient will undergo a careful history and physical examination to rule out major cardiac, pulmonary or renal disease. All subjects will undergo: 1. Baseline biopsy of a secondary tumor or a metastatic tumor at the time of cryoablation. Tumor specimens will also be collected during surgery (cytoreductive, partial or total nephrectomy). 2. One or more optional biopsies at day 53, day 106 and day 169 after cryoablation. 3. Blood samples: will be collected at baseline before or at time of cryoablation, at the end of the second cycle of pembrolizumab treatment and during surgery (cytoreductive, partial or total nephrectomy) for evaluation of biomarkers and pharmacokinetic analyses. 4. Complete radiologic assessment in the form of CT scan at baseline and a CT scan after the third cycle of pembrolizumab followed by routine imaging every 6 weeks as is consistent with the standard of care for mRCC. 5. Routine laboratory analysis: basic metabolic panel (BMP), liver function panel (LFTs) and complete blood count (CBC), will be collected prior to each cycle of pembrolizumab administration and at the time of cryoablation and cytoreductive or partial/total nephrectomy. Cryoablation: Patients will be asked to have nothing by mouth during at least 8 hours prior to ablation. Patients will only be taken for cryoablation if INR is \<1.5, PTT is within normal limits and platelet count is greater than 50,000/microL. Preoperative imaging, namely contrast enhanced CT scan, will be used to assess the tumor proximity to local structures. Number of cryoprobes utilized will be determined by the size, geometry, and morphology of the primary tumor. CT guidance will be used to place the cryoprobes 1 to 1.5 cm apart. Two 10 minute freeze cycles with an intervening 8 minute thawing period will be used in accordance with data indicating improved efficacy with the double-freeze thaw cycle. The size of the iceball created will be consistent with a tumor-free margin of at least 5-10 mm. CT scans at 3-4 minute intervals will be used to assure adequate margins. Pembrolizumab: Pembrolizumab treatment will begin 1 day following cryoablative treatment and will continue until a complete tumor remission, disease progression, unacceptable toxicity, subject refusal, or subject death due to any cause. Surgery After 3 cycles (9 weeks) of pembrolizumab therapy, patients will undergo partial/ radical or cytoreductive nephrectomy of the primary renal tumor. Duration of follow-up Subjects will be followed for a total of 24 months. Subjects removed from treatment due to unacceptable adverse events will be followed until resolution or stabilization of adverse event. Follow up will be every 8 weeks (+2 weeks) from study registration with imaging studies and physical exam every 8 weeks for the first 8 months, then every 12 weeks (+ 2 weeks) until 24 months.

Conditions

• Renal Cell Carcinoma
• Metastatic Kidney Cancer

Interventions

Type	Name	Description
DRUG	Pembrolizumab Injection [Keytruda]	Same as arm description
PROCEDURE	Cryoablation	Cryoablation uses liquid argon in metal needles to freeze tumors. Tumor cells are ruptured due to the forming ice crystals and die. Cryoablation is standardly used in tumors less then 4cm in diameter.
PROCEDURE	Nephrectomy	Nephrectomy is the surgical excision of either the entire kidney or a small portion of the kidney. Nephrectomy is standardly used to treat renal cell cancer.

Timeline

• Start date: 2017-07-01
• Primary completion: 2018-10-17
• Completion: 2018-10-17
• First posted: 2017-06-16
• Last updated: 2021-04-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study