Ignite Creation Date:
2025-12-24 @ 1:14 PM
Ignite Modification Date:
2026-04-17 @ 10:31 PM
Study NCT ID:
NCT02489695
Status:
COMPLETED
Last Update Posted:
2022-09-06
First Post:
2015-06-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Axitinib in1st Line Treatment for Patients With Advanced or Metastatic Papillary Renal Cell Carcinoma
Sponsor:
Centre Leon Berard
Organization:
Study Overview
Official Title:
Multicenter Phase II Study of Axitinib in First Line Treatment for Patients With Locally Advanced or Metastatic Papillary Renal Cell Carcinoma (PRCC)
Status:
COMPLETED
Status Verified Date:
2022-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AXIPAP
Brief Summary:
Multicenter, single arm, phase II study using a A'Hern single-stage procedure in patients with locally advanced or metastatic papillary renal cell carcinoma (PRCC) in first-line treatment.
Detailed Description:
Renal cell carcinoma (RCC) accounts for 2-3% of all adult malignancies worldwide, representing the seventh most common cancer in men and the ninth in women. The annual incidence is more than 337 000 cases and around 140 000 persons die every year. Half of patients with RCC are going to develop metastases, either with synchronous metastatic sites (25%) or during the follow up (25%).
Papillary renal cell carcinoma (PRCC) represents 10-15% of RCC and is characterized by a cytogenetic profile distinct from other types of renal cancer. Histologically, PRCC could be separated in 2 distinct subtypes: type 1 and type 2.
Vascular endothelial growth factor (VEGF) is a potent induction factor, playing a central role in angiogenesis and vascular permeability of tumor tissues. It binds to three specific receptors: VEGFR-1, VEGFR-2 and VEGFR-3, which are thus implicated in pathologic angiogenesis, tumor growth and metastatic progression of cancer. Patients with papillary histology demonstrated high expression of VEGF and VEGFR-2, making VEGF-targeted therapy an attractive therapeutic option.
Recently, several studies have been developed to assess VEGF targeted therapy in patients with PRCC, mostly with sunitinib and with poor results (median progression-free survival (PFS) around 6 months).
Axitinib is a potent, selective second-generation inhibitor of all three VEGF receptors. By inhibiting VEGF-mediated endothelial cell proliferation and survival, axitinib inhibits angiogenesis and tumor growth.
In phase II trials, axitinib has shown anti-tumor activity with well-tolerated clinical safety profile in patients with advanced solid tumors, including RCC.
Axitinib has been approved for the second-line treatment of advanced RCC on the basis of the pivotal randomized phase III AXIS trial results. 723 patients were enrolled and randomly assigned to receive axitinib or sorafenib. The median PFS assessed by independent review committee was 6.7 months with axitinib compared to 4.7 months with sorafenib (hazard ratio 0.665; 95% CI 0.544-0.812; one-sided p\<0.0001).
In all studies, the safety analysis showed a good tolerance of axitinib. The most common adverse reactions (occurring in \>20% of treated subjects) were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia and hand-foot skin reaction. Dose discontinuations were reported in 4% of patients with axitinib vs. 8% with sorafenib.
Little clinical data regarding the efficacy of recently developed VEGF targeted therapies in first-line treatment of PRCC is available. To date, there is no standard treatment, and evaluation of efficacy of the new targeted agents is clearly needed.
The purpose of this study is to evaluate the efficacy and safety of axitinib in first-line treatment of patients with papillary renal cell carcinoma.
Axitinib inhibits angiogenesis and vascular permeability in tumor tissues, leading to inhibition of tumor growth.
Axitinib has shown antitumor activity in patients with RCC in phase II and III clinical trials.
VEGF inhibitors are currently used in PRCC treatment, with disappointing results. Axitinib is more potent and selective against the VEGFR family compared with sorafenib and sunitinib in biochemical assays, and could have a similar efficacy with lesser toxicities, therefore may provide a clinical benefit in patients with PRCC.
Papillary renal cell carcinoma (PRCC) represents 10-15% of RCC and is characterized by a cytogenetic profile distinct from other types of renal cancer. Histologically, PRCC could be separated in 2 distinct subtypes: type 1 and type 2.
Vascular endothelial growth factor (VEGF) is a potent induction factor, playing a central role in angiogenesis and vascular permeability of tumor tissues. It binds to three specific receptors: VEGFR-1, VEGFR-2 and VEGFR-3, which are thus implicated in pathologic angiogenesis, tumor growth and metastatic progression of cancer. Patients with papillary histology demonstrated high expression of VEGF and VEGFR-2, making VEGF-targeted therapy an attractive therapeutic option.
Recently, several studies have been developed to assess VEGF targeted therapy in patients with PRCC, mostly with sunitinib and with poor results (median progression-free survival (PFS) around 6 months).
Axitinib is a potent, selective second-generation inhibitor of all three VEGF receptors. By inhibiting VEGF-mediated endothelial cell proliferation and survival, axitinib inhibits angiogenesis and tumor growth.
In phase II trials, axitinib has shown anti-tumor activity with well-tolerated clinical safety profile in patients with advanced solid tumors, including RCC.
Axitinib has been approved for the second-line treatment of advanced RCC on the basis of the pivotal randomized phase III AXIS trial results. 723 patients were enrolled and randomly assigned to receive axitinib or sorafenib. The median PFS assessed by independent review committee was 6.7 months with axitinib compared to 4.7 months with sorafenib (hazard ratio 0.665; 95% CI 0.544-0.812; one-sided p\<0.0001).
In all studies, the safety analysis showed a good tolerance of axitinib. The most common adverse reactions (occurring in \>20% of treated subjects) were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia and hand-foot skin reaction. Dose discontinuations were reported in 4% of patients with axitinib vs. 8% with sorafenib.
Little clinical data regarding the efficacy of recently developed VEGF targeted therapies in first-line treatment of PRCC is available. To date, there is no standard treatment, and evaluation of efficacy of the new targeted agents is clearly needed.
The purpose of this study is to evaluate the efficacy and safety of axitinib in first-line treatment of patients with papillary renal cell carcinoma.
Axitinib inhibits angiogenesis and vascular permeability in tumor tissues, leading to inhibition of tumor growth.
Axitinib has shown antitumor activity in patients with RCC in phase II and III clinical trials.
VEGF inhibitors are currently used in PRCC treatment, with disappointing results. Axitinib is more potent and selective against the VEGFR family compared with sorafenib and sunitinib in biochemical assays, and could have a similar efficacy with lesser toxicities, therefore may provide a clinical benefit in patients with PRCC.
Study Oversight
Has Oversight DMC:
False
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| ET14-090 | OTHER | Centre Léon Bérard | View |