Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06642220
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-06
Brief Title:
Ablative Radioembolization of Renal Cell Carcinoma Trial
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Ablative Yttrium-90 Radioembolization Therapy for Non-Metastatic Renal Cell Carcinoma ARRCC Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ARRCC
Brief 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 40 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
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 81610 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 lt 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 gt 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 gt 4 cm however long term outcomes have not been established and those ablations carry higher risks of major bleeding complications than ablation of tumours lt 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 andor 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 tumors arterial bed deposits radiation dose within 25 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 eg 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 gt400 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 ie 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 2500 Bqbead vs 50 Bqbead 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 1050 Gy into a 15 cm RCC without any reported adverse events
Planned Study
A single-centre phase III clinical trial is proposed to evaluate the oncologic efficacy of Y-90 radioembolization treatment within the kidney for patients with large gt40 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
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 lt 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 gt 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 gt 4 cm however long term outcomes have not been established and those ablations carry higher risks of major bleeding complications than ablation of tumours lt 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 andor 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 tumors arterial bed deposits radiation dose within 25 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 eg 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 gt400 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 ie 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 2500 Bqbead vs 50 Bqbead 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 1050 Gy into a 15 cm RCC without any reported adverse events
Planned Study
A single-centre phase III clinical trial is proposed to evaluate the oncologic efficacy of Y-90 radioembolization treatment within the kidney for patients with large gt40 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None