Entry Detail
| General information | |
| Database: | DB00470 |
| Objective: | Preservation of renal function is prioritized during surgical management of localized renal cell carcinoma. VEGF targeted agents can downsize tumors in metastatic renal cell carcinoma and may do the same in localized renal cell carcinoma, allowing for optimal preservation of renal parenchyma associated with partial nephrectomy. |
| Authors: | Rini BI, et al |
| Title: | a phase II Study of Pazopanib in Patients with Localized Renal Cell Carcinoma to Optimize Preservation of Renal Parenchyma. |
| Journal: | J Urol. |
| Year: | 2015 |
| PMID: | 25813447 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | pazopanib |
| Target: | Plateletderived growth factor receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 |
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | clear cell renal carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II Study |
| Key Patients Feature: | Study eligibility criteria included patients with localized, biopsy proven clear cell RCC with a need for optimalpreservation of renal parenchyma based on 1) RN or PNwould yield GFR less than 30 ml/minute/1.73 m2 and/or2) anticipated increased risk of morbidity with PN due tohigh complexity (R.E.N.A.L. score 10 to 12) or hilar tumorlocation. Additional eligibility criteria included ECOG(Eastern Cooperative Oncology Group) performance status 0 or 1 and adequate organ function. Study exclusioncriteria were prior systemic therapy for RCC, evidence ofmetastatic disease, bleeding diathesis or coagulopathy(hematuria allowed), significant cardiovascular disease, prolonged QT interval or hypertension that could not becontrolled medically |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Pazopanib (800 mg once daily) was administered for 8 to 16 weeks with repeat imaging at completion of therapy, follotheyd by surgery. |
| Primary End Point: | the percentage of patients who could undergo PN after pazopanib therapy. |
| Secondary End Point: | the amount of vascularized parenchyma that could be saved with surgery after pazopanib therapy compared to pretherapy assessment. |
| Patients Number: | 25 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Of index lesions 80% were high complexity and 56% of patients had a solitary kidney. Patients received a median of 8 weeks of pazopanib. The median interval from treatment start to surgery was 10.6 weeks. R.E.N.A.L. score decreased in 71% of tumors and 92% of patients experienced a reduction in tumor volume. Six of 13 patients for whom partial nephrectomy was not possible at baseline were able to undergo partial nephrectomy after treatment. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | No CTCAE grade 4/5 AEs were observed. A total of 16 patients (64%) reported grade 3 AEs, primarily hypertension in 9 (36%) and elevated liver enzymes in 5 (20%). Perioperative events included 7 patients requiring blood transfusion, of whom one required embolization of a branch artery. There were no Clavien grade 4 or 5 perioperative AEs. Five patients had urine leaks postoperatively with 4 treated conservatively and a stent was placed to facilitate healing in 1. There were no thromboembolic events in this series. Wound infection occurred in 2 patients (8%) but fascial dehiscence was not encountered. In 1 case lymphangioembolization for chylous ascites failed but the condition resolved with conservative management after 10 weeks. |
| Conclusions: | Neoadjuvant pazopanib resulted in downsizing localized renal cell carcinoma, allowing for improved preservation of renal parenchyma and enabling partial nephrectomy in a select subset of patients who would otherwise require radical nephrectomy. |