This study has been transitioned to CTIS with ID 2024-515825-27-00 check the CTIS register for the current data. To investigate efficacy of neoadjuvant axitinib and avelumab in patients with localized renal cell carcinoma with moderate to high risk…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study is the rate of partial remission following
neoadjuvant axitinib and avelumab
Secondary outcome
1. Safety and adverse events of the combination of axitinib with avelumab
2. Clavien Dindo classification of surgical morbidity
3. Long term follow up with DFS, OS, rate of metastasis and local recurrence
4. Translational research
Background summary
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).
Vascular endothelial growth factor receptor (VEGFR)-targeted therapy has
improved progression free survival (PFS) and OS in metastatic RCC. Recently,
immunotherapy has shown superior OS when compared to everolimus in patients
with metastatic RCC. Immune checkpoint inhibitors are currently being
investigated in combination, or with VEGF-targeted therapy in patients with
previously untreated metastatic RCC against the current standard, sunitinib.
However, preclinical and early clinical research suggests that there is
significantly greater therapeutic efficacy of neoadjuvantimmunotherapies
instead of an adjuvant approach to eradicate distant metastases following
primary tumor resection. This has resulted in several neoadjuvant phase I/II
studies which are currently ongoing. 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. We propose a phase II study of the combination of axitinib
with avelumab as neoadjuvant therapy in patients with high-risk non-metastatic
RCC.
Study objective
This study has been transitioned to CTIS with ID 2024-515825-27-00 check the CTIS register for the current data.
To investigate efficacy of neoadjuvant axitinib and avelumab in patients with
localized renal cell carcinoma with moderate to high risk of recurrence .
Study design
The study is designed as a single-arm, open label, monocenter phase II trial of
neoadjuvant axitinib and avelumab followed by complete surgical resection of
the kidney in patients with intermediate to high-risk locally advanced
clear-cell RCC
Intervention
6 cycles of neoadjuvant axitinib and avelumab followed by nephrectomy
Study burden and risks
Patients will receive extra treatments that will take a total of 12 weeks. The
patients need to return to the hospital more often because of the neoadjuvant
treatment. The patient can experience side effects due to the neoadjuvant
treatment
Plesmanlaan 121
Amsterdam 1066CX
NL
Plesmanlaan 121
Amsterdam 1066CX
NL
Listed location countries
Age
Inclusion criteria
• Signed and written informed consent
• Male or female patients age >= 18 years
• Histologically confirmed diagnosis of non-metastatic clear-cell renal cell
carcinoma of intermediate to high risk with completely resectable primary
tumours.
• World Health Organization (WHO) performance status of 0-1.
• Adequate coagulation function as defined in protocol
• Adequate hematological function as defined in protocol
• Adequate hepatic function as defined in protocol
• Adequate renal function as defined in protocol
• Negative serum pregnancy test at screening for women of childbearing
potential.
Exclusion criteria
•Renal tumors of low risk or M1
• Clinically significant gastrointestinal abnormalities that may affect
absorption of investigational product
• Major surgery or trauma within 28 days prior to first dose of investigational
product and/or presence of any non-healing wound, fracture, or ulcer
• Administration of any non-oncologic investigational drug prior to receiving
the first dose of study treatment
• Active autoimmune disease that might deteriorate when receiving an
immunostimulatory agent
• Known severe hypersensitivity reactions to monoclonal antibodies
• positive test for HBV or HCV
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-515825-27-00 |
| EudraCT | EUCTR2017-004161-27-NL |
| CCMO | NL63455.031.17 |
| Other | nummer volgt |