Phase II Study of Axitinib Intensification Plus Nivolumab Compared to Nivolumab Alone After Induction With Nivolumab Plus Ipilimumab in mRCC Patients Without Previous Complete Response (AxIn Study).
This phase II open label trial randomized patients who completed the induction with nivolumab plus ipilimumab without complete response or progressive disease will be randomized 1:1 to receive axitinib in addition to nivolumab (Arm A) or continue with nivolumab alone (Arm B).Treatment will be continued until progression of disease, unacceptable toxicity, patient's refusal, or physician decision whichever occurred first.
• Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype and candidate to receive nivolumab after nivolumab plus ipilimumab induction as per standard clinical practice.
• Completion of the induction of nivolumab and ipilimumab without toxicity ≥ G2 and no complete response or progressive disease.
• Male or female subjects aged ≥ 18 years
• Available tumor tissue sample.
• At least one measurable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group performance status 0 or 1.
• Adequate organ and bone marrow function based upon meeting all of the following laboratory criteria within 10 days before the start of treatment:
∙ Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L)
‣ Platelets ≥ 100,000/mm3 (≥ 100 GI/L).
‣ Haemoglobin ≥ 9 g/dL (≥ 90 g/L).
‣ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3.0 × upper limit of normal.
‣ Total bilirubin ≤ 1.5 × the upper limit of normal. For subjects with Gilbert's disease ≤ 3 mg/dL (≤ 51.3 µmol/L).
‣ Serum creatinine ≤ 2.0 × upper limit of normal or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockroft-Gault.
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
• Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of study treatment.
⁃ Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrhoeic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antioestrogens, low body weight, ovarian suppression or other reasons.