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

NCT03341845

Last updated date
Study Location
Antoni van Leeuwenhoek
Amsterdam, , 1066CX, Netherlands
Contact
003120512

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Renal Cell Carcinoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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

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Advanced Information
Descriptive Information
Brief Title  ICMJE Neoadjuvant AXITINIB and AVELUMAB for Patients With Localized Clear-cell RCC
Official Title  ICMJE Neoadjuvant AXITINIB and AVELUMAB for Patients With Localized Clear-cell RCC and a Moderate to High Risk
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
simon's two stage design
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Renal Cell Carcinoma
Intervention  ICMJE
  • Drug: Axitinib
    axitinib in combination with avelumab
  • Drug: Avelumab
    axitinib in combination with avelumab
Study Arms  ICMJE Experimental: axitinib and avelumab
axitinib 5MG BID and avelumab 10mg/kg Q2W
Interventions:
  • Drug: Axitinib
  • Drug: Avelumab
Publications * Bex A, van Thienen JV, Schrier M, Graafland N, Kuusk T, Hendricksen K, Lagerveld B, Zondervan P, van Moorselaar JA, Blank C, Wilgenhof S, Haanen J. A Phase II, single-arm trial of neoadjuvant axitinib plus avelumab in patients with localized renal cell carcinoma who are at high risk of relapse after nephrectomy (NEOAVAX). Future Oncol. 2019 Jul;15(19):2203-2209. doi: 10.2217/fon-2019-0111. Epub 2019 Apr 26. Erratum in: Future Oncol. 2019 Aug;15(22):2667.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 9, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2025
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Axel Bex, MD003120512 ext 9111[email protected]
Contact: Hans van Thienen, MD003120512 ext 9111[email protected]
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03341845
Other Study ID Numbers  ICMJE N17JAV
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Undecided
Plan Description:decided by PI at each request for data
Responsible Party The Netherlands Cancer Institute
Study Sponsor  ICMJE The Netherlands Cancer Institute
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Axel Bex, MDNKI-AvL
PRS Account The Netherlands Cancer Institute
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP