Prospective, randomized, neoadjuvant phase II study with combination immuno-oncology in primary clear cell renal cell cancer at risk for recurrence or distant metastases (NESCIO-trial; M21NSC; CA209-6DJ)
- Conditions
- clear cell renal cell carcinoma10038364kidney cancer
- Registration Number
- NL-OMON52016
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 46
• Adults at least 18 years of age
• World Health Organization (WHO) Performance Status 0 or 1
• Histologically confirmed resectable clear cell RCC (measurable according to
RECIST 1.1), that can be biopsied, and no history of distant metastases
• Intermediate to high risk will be based on clinical TNM and biopsy nuclear
grade. These are:
1. cT1b-cT2a grade 4 cN0 cM0
2. cT2b grade 3-4 cN0 cM0
3. cT3 any grade cN0 cM0
4. cT4 any grade cN0 cM0
5. cT any cN1 (fully resectable) cM0
• No other malignancies, except adequately treated and a cancer-related
life-expectancy of more than 5 years
• Patient willing to undergo triple tumor biopsies and extra blood withdrawal
during screening and in case of relapse
• No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1, or LAG-3
• No immunosuppressive medications within 2 weeks prior start immunotherapy
• Screening laboratory values must meet the following criteria: WBC >=
2.0x109/L, Neutrophils >=1.5x109/L, Platelets >=100 x109/L, Hemoglobin >=5.5
mmol/L, Creatinine <=1.5x ULN, AST <= 1.5 x ULN, ALT <= 1.5 x ULN, Bilirubin <=1.5
X ULN, normal CK and Troponin T, normal LDH
• Women of childbearing potential must use appropriate method(s) of
contraception. They should use an adequate method to avoid pregnancy for 23
weeks (30 days plus the time required for nivolumab to undergo five half-lives)
after the last dose of investigational drug
• Women of childbearing potential must have a negative serum or urine pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours
prior to the start of study treatment
• Women who are not of childbearing potential (i.e., who are postmenopausal),
or surgically sterile as well as azoospermic men do not require contraception
• Patient is capable of understanding and complying with the protocol
requirements and has signed the Informed Consent document.
• Distantly metastasized RCC • Brain metastases (based on symptoms) • Non-clear
cell RCC • No measurable lesion according to RECIST 1.1 • Subjects with any
active autoimmune disease or a documented history of autoimmune disease, or
history of syndrome that required systemic steroids or immunosuppressive
medications, except for subjects with vitiligo or resolved childhood
asthma/atopy • Prior CTLA-4 or PD-1/PD-L1 or LAG-3 targeting immunotherapy •
Radiotherapy prior or post-surgery • Patients will be excluded if they test
positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus
ribonucleic acid (HCV antibody), indicating acute or chronic infection; if
treated and being at least one year free from HCV patients are allowed to
participate • Patients will be excluded if they have known history of testing
positive for human immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome (AIDS) • Allergies and Adverse Drug Reactions (like
mastocytosis) • History of severe hypersensitivity reaction to any monoclonal
antibody • Underlying medical conditions that, in the Investigator's opinion,
will make the administration of study drug(s) hazardous or obscure the
interpretation of toxicity or adverse events; • Pregnant or nursing •
Concurrent medical condition requiring the use of immunosuppressive
medications, or immunosuppressive doses of systemic or absorbable topical
corticosteroids; • Use of other investigational drugs before study drug
administration 30 days and 5 half-times before study inclusion
Relatlimab-specific exclusion criteria • Participants with history of
myocarditis, regardless of etiology. • Troponin T (TnT) > 2 × institutional
ULN. Participants with TnT levels between > 1 to 2 × ULN will be permitted if a
repeat levels within 24 hours are <= 1 ULN. If TnT levels are between >1 to 2 ×
ULN within 24 hours, the participant may undergo a cardiac consultation and be
considered for treatment, following cardiologist recommendation. When repeat
levels within 24 hours are not available, a repeat test should be conducted as
soon as possible. If TnT repeat levels beyond 24 hours are < 2 × ULN, the
participant may undergo a cardiac consultation and be considered for treatment,
following cardiologist recommendation. Notification of the decision to enroll
the participant following cardiologist recommendation has to be made to the BMS
Medical Monitor or designee. • Left ventricular ejection fraction (LVEF)
assessment with documented LVEF < 50% by either transthoracic echocardiogram
(TTE) or multigated acquisition (MUGA) scan (TTE preferred test) within 6
months prior to start of study treatment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The rate of pathological responses following different neoadjuvant<br /><br>immunotherapy combinations in high-risk non-metastatic clear cell RCC in an<br /><br>adaptive trial design and the safety and feasibility of neoadjuvant IO approach<br /><br>in high-risk non-metastatic clear cell renal cell cancer patients </p><br>
- Secondary Outcome Measures
Name Time Method