Neoadjuvant AXITINIB plus AVELUMAB for patients with localized RCC and a moderate to high risk of recurrence

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-07-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515825-27-00

EudraCT number

2017-004161-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To investigate efficacy of neoadjuvant axitinib and avelumab in patients with localized renal cell carcinoma with moderate to high
risk of recurrence

Conditions and MedDRA coding

renal cell carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male or female patients age ≥ 18 years
2. Signed and written informed consent
3. Histologically confirmed diagnosis of non-metastatic clear-cell renal cell carcinoma of intermediate to high risk with completely resectable primary tumours. For the purpose of this study intermediate to high risk will be based on clinical TNM and biopsy nuclear grade since the full pathological specimen is not available. These are: • cT1b-cT2a grade 4 cN0 cM0 • cT2b grade 3 cN0 cM0 • cT3a grade 3-4 cN0 cM0 • cT3b-cT4 any grade cN0 cM0 • cT any cN1 (fully resectable) cM0
4. World Health Organization (WHO) performance status of 0-1.
5. Adequate coagulation function
6. Adequate hematological function defined by absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 5,6 mmol/L (may have been transfused)
7. Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN for all subjects
8. Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula
9. Negative serum pregnancy test at screening for women of childbearing potential
10. Highly effective contraception for both male and female subjects if the risk of conception exists.

Exclusion criteria 22

1. Renal tumors of low risk
2. Metastatic disease, M1
3. Non-clear cell histology at biopsy
4. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:  Malabsorption syndrome  Major resection of the stomach or small bowel.
5. Corrected QT interval (QTc) > 480 msecs
6. History of any one or more of the following cardiovascular conditions within the past 6 months:  Cardiac angioplasty or stenting  Myocardial infarction  Unstable angina  Coronary artery bypass graft surgery  Symptomatic peripheral vascular disease  Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
7. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg].
8. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
9. 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 (procedures such as catheter placement not considered to be major surgery).
10. Evidence of active bleeding or bleeding diathesis.
11. 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.
12. 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
13. 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
14. Prior organ transplantation, including allogeneic stem cell transplantation
15. Significant acute or chronic infections including, among others: Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
16. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
17. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI CTCAE v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
18. Pregnancy or lactation
19. Known alcohol or drug abuse
20. All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the Investigator, might impair the subject’s tolerance of trial treatment
21. Any psychiatric condition that would prohibit the understanding or rendering of informed consent
22. Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this study is the rate of partial remission following neoadjuvant axitinib and avelumab.

Secondary endpoints 4

1. Safety and adverse events of the combination of axitinib with avelumab
2. Long term follow up with DFS, OS, rate of metastasis and local recurrence
3. Clavien Dindo classification of surgical morbidity
4. Translational research

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

A. Bex

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

A. Bex

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications