Prediction
Based on the provided evidence and the original eligibility criteria, here are the amended eligibility criteria for version 6:
**Inclusion Criteria:**
1.
Imaging results consistent with locally-advanced renal cell carcinoma (RCC) without evidence of metastatic disease with absence of adjacent organ invasion or retroperitoneal adenopathy (cT2-T3b, N0, M0).
2.
Candidate for partial or complete nephrectomy that extirpates all tumor tissue as part of treatment plan.
3.
Measurable disease as per RECIST version 1.1 (refer to Appendix 3).
4.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 (refer to Appendix 1).
5.
Adequate bone marrow and organ function demonstrated by:
- Absolute neutrophil count ≥ 1,000/mm³ (≥ 1.0 × 10⁹/L);
- Platelet count ≥ 100 × 10⁹/L (≥ 100,000 per mm³);
- ALT and AST ≤ 2.5 × ULN;
- Serum bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for patients with Gilbert Syndrome;
- Serum creatinine ≤ 1.5 × ULN, or creatinine clearance (CrCl) ≥ 50 mL/min (using the Cockcroft-Gault formula or following local institutional standards).
6.
≥ 18 years of age.
7.
Women of child-bearing potential (WOCBP) or men whose partner is a WOCBP agrees to use contraception while participating in this study, and for a period of 6 months following termination of study treatment.
8.
Completed informed consent process, including signing Institutional Review Board/Ethics Committee/Research Ethics Board (IRB/EC/REB) approved informed consent form.
9.
Willing to comply with clinical trial instructions and requirements.
**Exclusion Criteria:**
1.
Prior systemic anti-tumor treatment for RCC.
2.
Patients who are receiving any other investigational agents.
3.
Clinical status indicating that immediate surgery (within 6 weeks) is warranted regardless of whether neoadjuvant therapy is to be administered, as assessed by the treating surgeon.
4.
Inability to undergo baseline tumor biopsy.
5.
Active or prior documented autoimmune disease:
- Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis);
- Interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease;
- Other active or prior, documented autoimmune disease within the past 2 years.
**Note:** Patients with Type I diabetes, vitiligo, Grave’s disease, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
6.
Active or prior immunocompromising conditions:
- Current or prior use of immunosuppressive medication within 28 days before the first dose of study treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent dose of another corticosteroid;
- Known acute or chronic human immunodeficiency virus (HIV);
- History of primary immunodeficiency;
- History of allogeneic transplant.
7.
Known acute or chronic hepatitis B or hepatitis C.
8.
History of hypersensitivity to study treatment excipient.
9.
History of severe hypersensitivity reaction to any monoclonal antibody.
10.
Use of live vaccines against infectious disease (e.g., varicella) within 28 days of initiation of study therapy; killed vaccinations (e.g., influenza) are allowed at any appropriate time before and during the study.
11.
Uncontrolled arterial hypertension (> 150 mm Hg systolic or > 100 mm Hg diastolic) on multiple observations despite standard of care treatment.
12.
History of stroke or transient ischemic attack within the previous 6 months.
13.
Any of the following cardiac abnormalities:
- Unstable angina pectoris;
- Congestive heart failure ≥ NYHA (New York Heart Association Functional Classification) Class 3;
- QTc > 480 milliseconds;
- Left ventricular ejection fraction (LVEF) ≤ 40%.
14.
Concomitant medication known to cause prolonged QT which cannot be discontinued or changed to a different medication prior to enrollment (refer to Appendix 2).
15.
Known or suspected presence of another malignancy that could be mistaken for the malignancy under study during disease assessments.
16.
Pregnancy.
WOCBP must have a negative serum or urine pregnancy test documented within the screening period prior to start of study drug.
17.
Breast-feeding or planning to breast feed during the study or within 6 months after study treatment.
18.
Any serious illness, uncontrolled intercurrent illness, psychiatric illness, active or uncontrolled infection, or other medical history, including laboratory results, which, in the Investigator’s opinion, would be likely to interfere with the patient’s participation in the study, or with the interpretation of the results.
These amendments incorporate the evidence provided, particularly focusing on the inclusion and exclusion criteria related to the combination therapy with sitravatinib and nivolumab, while maintaining clinical accuracy and relevance.