NCT03341845

Neoadjuvant AXITINIB and AVELUMAB for Patients With Localized Clear-cell RCC

Neoadjuvant AXITINIB and AVELUMAB for Patients With Localized Clear-cell RCC and a Moderate to High Risk

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: The Netherlands Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

a monocenter, open label, single arm, phase II study of the combination of axitinib with avelumab as neoadjuvant therapy in patients with intermediate to high-risk non-metastatic RCC.

Detailed description

Renal cell carcinoma (RCC) accounts for 3% of adult malignancies and constitutes 95% of renal tumors. Surgical complete resection is currently the only curative treatment of RCC, including patients with locally advanced RCC or limited metastatic disease. However, these patients carry a high risk to develop locally recurrent disease and systemic progression. High risk patients with no evidence of disease following complete resection may therefore benefit from adjuvant and neo-adjuvant systemic treatment strategies which primarily aim to prolong disease free (DFS) and ultimately overall survival (OS). Neoadjuvant studies are a unique opportunity to further investigate the way in which immune checkpoint inhibition works and to identify predictors of treatment response. Recent research on intratumoral immune components after pretreatment of human renal cell carcinoma suggest a potential synergism for TKI with anti-PD-L1 therapy that could be exploited. In terms of downsizing tumours by pretreatment, axitinib has been shown to be more effective than sunitinib when comparing trials that have been performed with each drug. However, the immunemodulatory effect of axitinib has been ill defined. Since axitinib and anti-PD-L1 therapy would make for a potential synergism, two phase Ib dose-finding studies to evaluate safety, pharmacokinetics and pharmacodynamics of avelumab, an anti-PD-L1 monoclonal antibody, or pembrolizumab, an anti-PD1 monoclonal antibody, in combination with axitinib were performed. First results on response rate and safety profile presented at ESMO 2016 were promising with objective response rates of 67-70 % and toxicity profiles as seen with VEGFR-treatment. The investigator proposes a monocenter, open label, single arm, phase II study of the combination of axitinib with avelumab as neoadjuvant therapy in patients with intermediate to high-risk non-metastatic RCC. The statistical calculation of the primary endpoint is based on efficacy on the local tumour. The safety of this combination prior to surgery will be an important secondary endpoint.

Conditions

• Renal Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Axitinib	axitinib in combination with avelumab
DRUG	Avelumab	axitinib in combination with avelumab

Timeline

• Start date: 2018-03-28
• Primary completion: 2023-01-31
• Completion: 2025-01-31
• First posted: 2017-11-14
• Last updated: 2018-05-21

Locations

1 site across 1 country: Netherlands