AXITINIB for Metastatic renal cell carcinoma | Locally advanced renal cell carcinoma

Inclusion criteria

• {"criterion_text":"- Informed consent obtained before any study-specific procedures. Patients must be able to understand and be willing to sign a written informed consent\n- Women of childbearing potential and men must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. The investigator or a designated associate is requested to advise the subject how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommend method (or combination of methods) as per standard of care\n- Adequate bone-marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days of starting to study treatment: a)\tCreatinine value <2.5 mg/dl and creatinine clearance > 30 ml/min evaluated by the Cockcroft-Gault Formula. b)\tTotal bilirubin ≤1∙5 × the upper limit of normal (ULN); c)\tAlanine aminotransferase and aspartate aminotransferase ≤2 × ULN (≤5 × ULN for patients with liver involvement of their cancer); d)\tInternational normalized ratio (INR) and partial thromboplastin time (PTT) ≤1∙5 × ULN. Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no prior evidence of an underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care; e)\tPlatelet count ≥100 000/mm3, hemoglobin >9 g/dl, absolute neutrophil count >1,500/mm3; f)\tAlkaline phosphatase limit ≤2∙5 × ULN (≤5 × ULN for patients with liver involvement of their cancer).\n- Male or female patient ≥18 years of age\n- Histological or cytological documentation of renal cell carcinoma with predominantly clear cell histology\n- Evidence of primary renal cancer\n- Measurable or not measurable metastatic disease according to Response Evaluation Criteria in Solid Tumors criteria, version 1.1\n- Eastern Cooperative Oncology Group performance status of ≤1\n- Life expectancy of at least 9 months\n- Under treatment with SOC consisting in one anti-PD1 based therapy among axitinib + pembrolizumab or cabozantinib + nivolumab or lenvatinib + pembrolizumab or nivolumab alone after nivolumab + ipilimumab for at least 24 but not more than 52 weeks at the time of the signed informed consent and without evidence of progressive disease based on RECIST criteria v 1.1\n- Eligible to continue the combination of therapies for mRCC (or nivolumab alone in case of nivolumab + ipilimumab)"}

Exclusion criteria

• {"criterion_text":"- More than one treatment for metastatic or locally advanced renal cell carcinoma\n- Solitary kindney\n- Any contraindication to surgery or radiotherapy on primary renal tumor\n- Discontinuation (definitive) of one of the therapies for mRCC due to toxicity (previous discontinuation of ipilimumab in the ipilimumab + nivolumab combo is allowed).\n- Concurrent or previous cancer within 3 years before enrolment EXCEPT curatively treated cervical cancer in situ, non-melanoma skin cancer and pT2 prostate cancer with PSA<0.01 or non-muscle invasive bladder cancer\n- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before the signed informed consent\n- Pregnancy or breast-feeding. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before surgery or radiotherapy on primary tumor, and a negative result must be documented before start of treatment\n- Any cardiological condition among: a)\tCongestive heart failure of New York Heart Association class 3 or worse. b)\tUnstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study drug. c)\tCardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted). d)\tUncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg despite optimal medical management). e)\tArterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), pulmonary embolism within the 4 months before start of study.\n- Ongoing infection higher than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 grade 2\n- Known history of human immunodeficiency (HIV) virus infection or known history of chronic hepatitis B or C\n- Any autoimmune reaction or toxicity that contraindicates the use of anti-PD1 therapy\n- Seizure disorder requiring medication\n- Symptomatic metastatic brain or meningeal tumors unless the patient is >2 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also, the patient must not be undergoing acute steroid therapy or tapering (chronic steroid therapy is acceptable provided that the dose is stable for 1 month before and after screening radiographic studies).\n- History of organ allograft\n- Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event of CTCAE grade 3 or higher within 4 weeks of start of study medication\n- Non-healing wound, ulcer, or bone fracture\n- Renal failure requiring hemodialysis or peritoneal dialysis\n- Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his or her compliance in the study"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint of the study is to assess the difference in overall survival (OS) between patients who receive or not the deferred citoreductive nephrectomy (CN) while on therapy with SOC for mRCC","definition_or_measurement_approach":"Assessment of difference in overall survival (OS) between patients who receive or do not receive deferred cytoreductive nephrectomy while on standard-of-care (SOC) therapy for metastatic renal cell carcinoma (mRCC)."}

Secondary endpoints

• {"endpoint_text":"- To assess the difference in overall survival (OS) between patients who receive or not the deferred citoreductive nephrectomy (CN) while on therapy with SOC for mRCC from the beginning of the anti-PD1-based therapy","definition_or_measurement_approach":"Overall survival (OS) measured from the beginning of anti-PD1-based therapy comparing groups with or without deferred CN."}
• {"endpoint_text":"- To assess the difference in progression-free survival (PFS) between patients who receive or not the deferred citoreductive nephrectomy (CN) while on therapy with SOC for mRCC","definition_or_measurement_approach":"Progression-free survival (PFS) comparison between groups with or without deferred CN (based on RECIST v1.1 criteria as used elsewhere in the protocol)."}
• {"endpoint_text":"- To assess the difference in overall survival (OS) between patients who receive or not the radiotherapy on primary tumor while on therapy with SOC for mRCC among those with primary tumor up to 4 cm at randomization","definition_or_measurement_approach":"Overall survival (OS) comparison in subgroup with primary tumor ≤4 cm randomized to radiotherapy on primary tumor versus no radiotherapy, while on SOC."}
• {"endpoint_text":"- To assess the difference in progression-free survival (PFS) between patients who receive or not the radiotherapy on primary tumor while on therapy with SOC for mRCC among those with primary tumor up to 4 cm at randomization.","definition_or_measurement_approach":"Progression-free survival (PFS) comparison in the specified radiotherapy subgroup."}
• {"endpoint_text":"- To evaluate the safety of the CN and RT on primary tumor among patients receiving SOC for mRCC. Adverse events will be graded according to NCI CTCAE version 5.0","definition_or_measurement_approach":"Safety assessed by adverse events graded per NCI CTCAE v5.0."}
• {"endpoint_text":"- To evaluate the quality of life before and after 8 weeks from the CN or RT on primary tumor among patients receiving SOCfor mRCC evaluated by the questionnaires EQ-5D-5L and FKSI-19 and the surgical complications by the Clavien-Dindo classification","definition_or_measurement_approach":"Quality of life assessed using EQ-5D-5L and FKSI-19 questionnaires before and 8 weeks after CN or RT; surgical complications classified by Clavien-Dindo."}
• {"endpoint_text":"- Translational endpoint: To describe as different strategies (CN or RT) affect the patient’s proteome and the correlation between the proteome profile at baseline or its changes with the outcome (i.e.: PFS and OS) to SOC","definition_or_measurement_approach":"Proteomic analyses comparing baseline and changes after CN or RT and correlating proteome profiles with clinical outcomes (PFS and OS)."}
• {"endpoint_text":"- Translational endpoint: •\tTo describe as the expression of some markers such as PD-L1, PBRM1, BAP1, and presence of CD4 and C8 lymphocytes correlated with the outcome (i.e.: PFS and OS) in the different groups of patients","definition_or_measurement_approach":"Immunohistochemical and cellular marker expression (PD-L1, PBRM1, BAP1, CD4, CD8) correlated with clinical outcomes (PFS, OS)."}

Italy

Earliest CTIS Part Ii Submission Date

20-02-2025

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

270

Number Of Sites

33

Number Of Participants

409

Primary sponsor

Full Name

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Contract research organisations

Name

Clinical Research Technology S.r.l.

Responsibilities

Site contract negotiation; Site contact; additional sponsor duties (codes: 3,5,6,7,8,12) as listed in CTIS third parties

Third parties

• {"country":"United States","full_name":"Somalogic Operating Co. Inc.","duties_or_roles":"PROTEOMIC ANALYSIS","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Italy","full_name":"Clinical Research Technology S.r.l.","duties_or_roles":"Sponsor duties codes: 12; 15 (Site contract negotiation, Site contact); 3; 5; 6; 7; 8","organisation_type":"Pharmaceutical company"}