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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03341845
Recruitment Status : Recruiting
First Posted : November 14, 2017
Last Update Posted : May 21, 2018
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Drug: Axitinib Drug: Avelumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: simon's two stage design
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant AXITINIB and AVELUMAB for Patients With Localized Clear-cell RCC and a Moderate to High Risk
Actual Study Start Date : March 28, 2018
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : January 31, 2025

Arm Intervention/treatment
Experimental: axitinib and avelumab
axitinib 5MG BID and avelumab 10mg/kg Q2W
Drug: Axitinib
axitinib in combination with avelumab

Drug: Avelumab
axitinib in combination with avelumab

Primary Outcome Measures :
  1. number of patients with partial remission [ Time Frame: week 12 of neoadjuvant treatment ]
    according to RECIST 1.1.

Secondary Outcome Measures :
  1. toxicity [ Time Frame: up to 90 days after end of treatment ]
    measured by number and grade of adverse events

  2. event free survival and overall survival [ Time Frame: assessed up to 10 years ]
    Time from registration to disease progression or death

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 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.
  • Highly effective contraception for both male and female subjects if the risk of conception exists.

Exclusion Criteria:

Renal tumors of low risk or M1

  • Non-clear cell histology at biopsy
  • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
  • Corrected QT interval (QTc) > 480 msecs
  • History of any of the cardiovascular conditions defined in the protocol within the past 6 months
  • Poorly controlled hypertension
  • History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
  • 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
  • Evidence of active bleeding or bleeding diathesis.
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  • Unable or unwilling to discontinue use of prohibited medications to be listed in protocol for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study
  • Treatment with any of the following anti-cancer therapies: chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of axitinib or avelumab
  • Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment
  • Prior organ transplantation, including allogeneic stem cell transplantation
  • Significant acute or chronic infections as defined in protocol
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
  • Known severe hypersensitivity reactions to monoclonal antibodies
  • Pregnancy or lactation
  • Known alcohol or drug abuse

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03341845

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Contact: Axel Bex, MD 003120512 ext 9111
Contact: Hans van Thienen, MD 003120512 ext 9111

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Antoni van Leeuwenhoek Recruiting
Amsterdam, Netherlands, 1066CX
Contact: Axel Bex, MD, PhD    0205129111   
Sponsors and Collaborators
The Netherlands Cancer Institute
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Principal Investigator: Axel Bex, MD NKI-AvL
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: The Netherlands Cancer Institute Identifier: NCT03341845    
Other Study ID Numbers: N17JAV
First Posted: November 14, 2017    Key Record Dates
Last Update Posted: May 21, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: decided by PI at each request for data

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Kidney Diseases
Urologic Diseases
Male Urogenital Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action