Ablative Radioembolization of Renal Cell Carcinoma Trial

Trial Title: Ablative Radioembolization of Renal Cell Carcinoma Trial

NCT ID: NCT06642220

Condition: Renal Cell Carcinoma (RCC)
Radioembolization

Conditions: Official terms:
Carcinoma
Carcinoma, Renal Cell

Conditions: Keywords:
renal cell carcinoma
radioembolization
selective internal radiation therapy (SIRT)
Y-90
Transarterial radioembolization (TARE)
RCC

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Device
Intervention name: Y-90 Selective Internal Radiation Therapy (SIRT)
Description: Y-90 radioembolization will be performed using glass spheres to treat non-metastatic RCC within the kidney.
Arm group label: Y-90 radioembolization treatment arm

Summary: Renal cell carcinoma (RCC), the most common type of kidney cancer, is typically treated with surgery; however, there is no established therapy for patients who are not surgical candidates and who have tumours greater than 4.0 cm in size. Selective internal radiation therapy (SIRT) or radioembolization using radioactive spheres containing 90-Yttrium (Y-90) is successful at treating large tumours with high doses of radiation within the liver and might be similarly effective for treating larger RCC tumours in patients, particularly those who are not surgical candidates. This prospective study will enroll 16 participants with RCC who are not candidates for surgery and treat them with Y-90 radioembolization using a high-dose therapy to see if it is an effective cancer therapy. Primary outcome will be RCC treatment response 1 year after the Y-90 radioembolization. Additionally, the safety, tolerability, and impact on kidney function of the therapy will be monitored for all participants. Patients will be followed for a total of 5 years to evaluate long-term outcome in cancer control and safety of the treatment.

Detailed description: Renal cell carcinoma (RCC) is the 8th most common cancer in the United States with 81,610 new cases diagnosed each year. 70% of new RCC cases are localized, non-metastatic at initial diagnosis; however, the risk of disease recurrence or progression to metastatic disease is higher for larger tumors and those with higher grade disease. The standard therapy for localized renal cell carcinoma (RCC) is surgery - either partial or radical nephrectomy. However, a substantial proportion of patients with RCC are not good surgical candidates, as the average age at diagnosis is 64-year-old, and obesity, smoking, hypertension and renal disease known risk factors. Currently there are no established standard-of-care therapies for patients who are not eligible for surgery. Unmet Clinical Need: There is a need to establish a definitive, minimally-invasive therapy patients for with large, non-metastatic RCC who are not surgical candidates. For non-surgical candidates with small RCC (< 4 cm or T1a) percutaneous ablation has been established as an effective minimally-invasive curative therapy. However, there is currently no minimally-invasive standard of care therapy for patients with larger localized RCC (> 4 cm) who are not surgical candidates, despite these patients being at higher risk for developing metastatic disease. Percutaneous ablation can be performed in patients with tumors > 4 cm; however, long term outcomes have not been established and those ablations carry higher risks of major bleeding complications than ablation of tumours < 4 cm. SBRT has shown some promising progression-free survival data for localized RCC; however, the radiation resistance of RCC cells require higher treatment doses to achieve cytotoxic effect. The achievable therapeutic dose of SBRT is currently limited to 30-60 Gy, often due to required reductions in the externally delivered dose to protect the commonly adjacent radiosensitive colon and/or small bowel that routinely abut the kidney. Selective internal radiation therapy (SIRT) or Yittrium-90 (Y-90) radioembolization is an endovascular therapy whereby beads loaded with the radioactive Yittrium-90 atom are injected through a catheter into the artery or arteries supplying the tumor to deliver the radiation dose internally. Radioactive decay of the Y-90 atom within the tumor's arterial bed, deposits radiation dose within 2.5 mm (maximum 11 mm) of the bead location. As such, the internal delivery of radiation, rather than external delivery of SBRT, allows for higher doses to be delivered to the tumour without exposing adjacent vulnerable organs to significant dose. Y-90 radioembolization has great success treating hepatocellular carcinoma (HCC) in the liver, commonly achieving tumor dose levels that are nearly ten times higher than SBRT (e.g. 300-500 Gy vs. 40-50 Gy). Furthermore, it has become a standard of care therapy for HCC with recent inclusion in the major international treatment guidelines. Y-90 tumor dosage of >400 Gy is the typical target with one major explant study showing complete pathological necrosis of HCC tumors when this dose was achieved8. RCC is a good potential disease target for Y-90 radioembolization as RCC is commonly hypervascular (similar to HCC) and the kidney is an end organ typically supplied by a single renal artery. Furthermore, the radioresistant tumour biology requires high radiation doses to achieve oncologic effect, which may be best achieved with the internal radiation delivery approach. Existing Safety Data of Y-90 in the kidney: Health Canada approval of Y-90 radioembolization is currently only for treatment of malignancies in the liver, where it is currently a standard of care therapy for treatment of HCC. The safety of Y-90 radioembolization in the kidney has been shown in preclinical studies as well as the RESIRT Phase I trial, which is the first and only human clinical trial of Y-90 radioembolization for RCC. The 21-patient RESIRT dose-escalation study had a heterogeneous patient population with both metastatic and non-metastatic RCC. The safety study showed no dose-limiting toxicity or reduction in renal function for treatment between 75-300 Gy; however, the secondary outcome of treatment response showed partial response in only 10% of patients without any complete response. The limited treatment response is potentially related to the administered dose being lower than the 400 Gy target used in the liver for complete pathologic necrosis. For HCC, complete pathologic necrosis from Y-90 SIRT requires an achieved tumour dose of ≥400 Gy. Within the liver, Y-90 administration of tumour doses ranging between 500-1000 Gy have been tolerated without serious adverse events. Given the known radioresistance of RCC, it is reasonable to expect that a similar or higher dose than HCC would be required to achieve an ablative therapy (i.e. ≥ 400 Gy). The RESIRT trial used resin beads for Y-90 delivery (SIRspheres, Australia) and arterial bed stasis (not permitting additional bead administration) occurred in 52% of the treated patients, which might have limited higher achievable RCC doses. Glass-sphere beads loaded with Y-90 (Therasphere, Boston Scientific) will be used instead of resin, which have higher Y-90 radiation activity per bead than the resin counterparts (2,500 Bq/bead vs. 50 Bq/bead). The higher activity per bead should overcome the maximum dose limitation in the RESIRT trial to achieve the 400+ Gy dose likely required to for complete pathologic necrosis. This is supported by a recent case report where radioembolization with Y-90 loaded on glass spheres achieved complete tumor response after delivering 1,050 Gy into a 1.5 cm RCC without any reported adverse events. Planned Study: A single-centre, phase I/II clinical trial is proposed to evaluate the oncologic efficacy of Y-90 radioembolization treatment within the kidney for patients with large (>4.0 cm), non-metastatic (localized) RCC who are not candidates or refuse the standard of care surgery. It is proposed that Y-90 radioembolization therapy with an ablative dose (≥400 Gy) into RCC within the kidney will achieve positive oncologic response and be tolerated clinically.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Patients willing to participate and provide written consent - Patients 18 years of age and older - Biopsy confirmed RCC > 4.0 cm and no renal vein or IVC involvement (T1b or T2 disease) - Not suitable for or declining standard of care nephrectomy or partial nephrectomy Exclusion Criteria: - Evidence of metastatic disease on CT or MRI - Severely impaired renal function (GFR ≤ 30) and not on dialysis - Bilateral RCC without plan for definitive therapy of the contralateral lesion - RCC that is locally recurrent at prior surgery or ablation site (new location in same or contralateral kidney is permitted) - Prior or concurrent kidney radiation therapy or systemic immunotherapy/TKI - Lung shunt with estimated lung radiation dose > 30 Gy for single dose or > 50 Gy total. - Contraindication to arterial renal angiogram, or both CT and MRI contrast medium - Life expectancy > 1 year - Pregnant or breast-feeding patient

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: London Health Sciences Centre - Victoria Hospital

Address:
City: London
Zip: N6A 5W9
Country: Canada

Contact:
Last name: Derek W Cool, MD PhD

Start date: January 1, 2025

Completion date: December 31, 2032

Lead sponsor:
Agency: Derek W. Cool
Agency class: Other

Collaborator:
Agency: Boston Scientific Corporation
Agency class: Industry

Source: Western University, Canada

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06642220