AXITINIB for Metastatic renal cell carcinoma

Inclusion criteria

• {"criterion_text":"- Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype and candidate to continue the standard of care with immunotherapy after nivolumab plus ipilimumab induction as per standard clinical practice.\n- 2. Completion of at least 2 cycles of the induction of nivolumab and ipilimumab without nivolumab-related toxicity that cannot allow the continuation of nivolumab and no complete response or progressive disease. Treatment with SOC ± axitinib should be started within 12 weeks from last dose of nivolumab/ipilimumab.\n- 3. Male or female subjects aged = 18 years\n- 4. Available tumor tissue sample.\n- 5. At least one measurable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.\n- 6. Eastern Cooperative Oncology Group performance status 0 or 1.\n- 7. Adequate organ and bone marrow function based upon meeting all of the following laboratory criteria within 10 days before the start of treatment: a) Absolute neutrophil count (ANC) = 1500/mm3 (= 1.5 GI/L) b) Platelets = 100,000/mm3 (= 100 GI/L). c) Haemoglobin = 9 g/dL (= 90 g/L). d) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 × upper limit of normal. e) Total bilirubin = 1.5 × the upper limit of normal. For subjects with Gilbert’s disease = 3 mg/dL (= 51.3 µmol/L). f) Serum creatinine = 2.0 × upper limit of normal or calculated creatinine clearance = 30 mL/min (= 0.5 mL/sec) using the Cockroft-Gault.\n- 8. Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.\n- 9. 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.\n- 10. 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."}

Exclusion criteria

• {"criterion_text":"- 1. Prior treatment with systemic therapy for advanced RCC with the exclusion of the induction of nivolumab and ipilimumab.\n- 2. Prior adjuvant or neoadjuvant therapy\n- 3. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis\n- 4. Diagnosis of any non-RCC malignancy occurring within 2 years prior to the date of the start of treatment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix or low-grade prostate cancer with no plans for treatment intervention.\n- 5. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the start of treatment. Systemic treatment with radionuclides within 6 weeks before the start of treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.\n- 6. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before the start of treatment.\n- 7. \tConcomitant anticoagulation at therapeutic doses with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel). These are not allowed in case of randomization in the experimental arm, enrollment is allowed if clinician and patient agree to switch to low-molecular-weight heparin (LMWH) in case of randomization to axitinib + SOC arm. No restrictions to anticoagulants is applied for patients randomized in the SOC arm alone.\n- 8. In past 6 months: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack.\n- 9. Chronic treatment with corticosteroids or other immunosuppressive agents (with the exception of inhaled or topical corticosteroids or corticosteroids with a daily dosage equivalent = 10 mg prednisone if given for disorders other than renal cell cancer). Subjects with brain metastases requiring systemic corticosteroid are not eligible.\n- 10. The subject has uncontrolled, significant intercurrent or recent illness i\n- 11. Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 3 months before the start of treatment. Complete wound healing from major surgery must have occurred 1 month before the start of treatment and from minor surgery (e.g., simple excision, tooth extraction) at least 10 days before the start of treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.\n- 12. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 msec within 1 month before the start of treatment .\n- 13. Vaccination within 4 weeks of the first dose of axitinib and while on trials is prohibited except for administration of inactivated vaccines.\n- 14. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.\n- 15. Current use of immunosuppressive medication,\n- 16. Has a history of substance abuse or medical, psychological, or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results.\n- 17. Has illness or medical conditions that are unstable or could jeopardize the safety of the patient and his or her compliance in the study.\n- 18. Pregnant or lactating females.\n- 19. Inability to swallow tablets or capsules.\n- 20. Previously identified allergy or hypersensitivity to components of the study treatment formulations.\n- 21. Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption."}

Primary endpoints

• {"endpoint_text":"- •\tTo evaluate the overall response rate in patients treated with the axitinib in addiction to SOC compared to SOC alone.","definition_or_measurement_approach":"Overall response rate (ORR) assessed by tumor response evaluations; measurable disease per RECIST version 1.1 (RECIST v1.1 referenced in eligibility)."}

Secondary endpoints

• {"endpoint_text":"- •\tTo evaluate the efficacy of axitinib in addiction to SOC compared to SOC alone in terms of: a)\tProgression free survival b)\tOverall survival c)\tDepth of response d)\tDuration of response e)\tQuality of life","definition_or_measurement_approach":"Progression-free survival and overall survival measured as time-to-event endpoints (standard survival analyses). Depth and duration of response assessed by RECIST v1.1 tumor assessments. Quality of life assessed using patient-reported instruments (documents list EQ-5D-5L and NCCN-FKSI forms)."}
• {"endpoint_text":"- •\tTo evaluate the safety of axitinib in addiction to SOC compared to SOC alone","definition_or_measurement_approach":"Safety evaluated by collection and assessment of adverse events, laboratory tests and clinical assessments (standard safety monitoring; specific CTCAE not explicitly stated in the extracted record)."}

Italy

Earliest CTIS Part Ii Submission Date

01-02-2024

Latest Decision Or Authorization Date

21-04-2026

Processing Time Days

810

Number Of Sites

34

Number Of Participants

118

Spain

Earliest CTIS Part Ii Submission Date

24-07-2025

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

272

Number Of Sites

11

Number Of Participants

60

Primary sponsor

Full Name

Consorzio Oncotech

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy