Cardenilimab Combined With Lenvatinib in Patients With Perioperative Resectable Clear Cell Renal Cell Carcinoma.

Официальное название

The Efficacy and Safety of Cardonilizumab Combined With Lenvastinib in Perioperative Treatment of Resectable Renal Clear Cell Carcinoma-A Single-arm, Single-center, Exploratory Clinical Study

Обзор

This study is a single-arm, single-center, phase II clinical study. The main purpose is to evaluate the perioperative efficacy and safety of cardenilimab combined with lenvatinib in patients with resectable clear cell renal cell carcinoma. This study included a screening period, a treatment period, and a follow-up period. After completing the examination and assessment during the screening period, qualified subjects will enter the study treatment period after signing the informed consent form. Subjects should receive induction therapy and maintenance therapy in accordance with the protocol until there is disease progression on imaging as judged by the investigator based on RECIST 1.1 standards, intolerable toxicity, or the subject voluntarily requests to terminate study treatment or withdraws information. Agree, or the researcher determines that treatment needs to be terminated. (1) Primary research endpoint: Objective response rate (ORR) of primary tumor according to RECIST 1.1 criteria (2) Secondary research endpoint: 1. According to RECIST 1.1, as assessed by the investigator: (1) Progression-free survival (Progress Free Survival, PFS); (2) Overall survival (OS); 2. Type, incidence and severity of adverse events (AE) and serious adverse events (SAE) assessed in accordance with NCI-CTCAE 5.0 . 3. Pathological response rate (MPR), R0 resection rate 4. Based on Quality of Life QoL score.

Вмешательства

• Препарат cardonilizumab combined with renvastinib
  Preoperative: Cardenilimab: 10 mg/kg qd intravenously, one cycle every 21 days, administered on the first day of each cycle, a total of 4 cycles. Lenvatinib: Weight \<60kg, 8mg, once a day, orally, for 4 cycles Weight \>60kg, 12mg, once a day, orally, for a total of 4 cycles Surgery: The patient is receiving 4 cycles of cardenilimab + Standard radical nephrectomy was performed within 30-40 days after the end of lenvatinib treatment. Postoperative: Cardenilimab: 10 mg/kg qd intravenously, 1

Первичные конечные точки

• ObjectiveResponse Rate，ORR [Срок оценки: The proportion of patients whose tumor size reduction reaches predetermined limits and persists over]

Вторичные конечные точки (7)

• Overall survival，OS [Срок оценки: The time from randomization to death (from any cause)]
• Progress Free Survival，PFS [Срок оценки: The time between the start of randomization and the progression of tumor development (in any respect]
• Types, incidence, and severity of adverse event (AE) [Срок оценки: 28 days after the last dose of study treatment]
• Types, incidence, and severity of serious adverse event (SAE) [Срок оценки: 28 days after the last dose of study treatment]
• major pathologic response, MPR [Срок оценки: After neoadjuvant therapy, the percentage of surviving tumor cells in the tumor bed was less than 10]
• After neoadjuvant therapy, the percentage of surviving tumor cells in the tumor bed was less than 10 [Срок оценки: Standard radical nephrectomy]
• Quality of life score [Срок оценки: 28 days after the last dose of study treatment]

Критерии участия

Критерии включения

• Male or female patients: 18-75 years old;
• ECOG physical condition score: 0\~2 points;
• Histologically confirmed resectable non-metastatic clear cell carcinoma of the kidney (TNM staging criteria for renal carcinoma);
• Expected survival ≥12 weeks;
• Have not received systemic anti-tumor therapy before;
• Major organ function is normal, that is, relevant examination indicators within 14 days before randomization meet the following requirements: 1) Blood routine examination: a) hemoglobin ≥90 g/L (no blood transfusion within 14 days); b) Neutrophil count ≥1.5×109/L; c) Platelet count ≥100×109/L; 2) Biochemical examination: a) Total bilirubin ≤ 1.5×ULN (upper limit of normal value); b) Serum glutamic-pyruvic aminotransferase (ALT) or serum glutamic-oxalic aminotransferase (AST) ≤ 2.5×ULN; If there is liver metastasis, ALT or AST ≤ 5×ULN; c) Serum creatinine <1.5 times the upper limit of normal; Endogenous creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula); 3) Routine coagulation test: a) International Standardized ratio (INR) or prothrombin time (PT) ≤1.5 X ULN. b) Activated partial thromboplastin time (APTT) ≤1.5 x ULN. 4) Cardiac Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ 50%.
• Women of childbearing age must undergo a pregnancy test (serum or urine) within 7 days prior to inclusion, with a negative result, and be willing to use an appropriate method of contraception during the test period and for 8 weeks after the last dose of the test drug. For men, consent to use appropriate methods of contraception or surgical sterilization during the trial period and within 8 weeks after the last dose of the trial drug;
• The subjects voluntarily joined the study and signed the informed consent, with good compliance and follow-up.

Критерии исключения

• Other malignancies diagnosed within 5 years prior to administration, excluding radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radical resection of carcinoma in situ. If another malignant tumor or lung cancer is diagnosed more than 5 years before administration, pathological or cytological diagnosis of recurrent lesions is required.
• Currently participating in an interventional clinical study or receiving other drugs or investigational devices within 4 weeks prior to initial dosing;
• Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs that target another stimulus or synergistically inhibit T cell receptors (e.g. CTLA-4, OX-40, CD137);
• Received immunomodulatory drugs (thymosin, interferon, interleukin, etc.) within 2 weeks before the first dose, or received major surgical treatment within 3 weeks before the first dose;
• Have a history of bleeding, any bleeding event with a severity rating of CTCAE5.0 or higher occurring within 4 weeks prior to screening;
• Received solid organ or blood system transplantation;
• Clinically uncontrolled active infections, including but not limited to acute pneumonia;
• History of idiopathic pulmonary fibrosis, institutional pneumonia (such as bronchiolitis obliterans), and drug-related pneumonia;
• Uncontrolled or symptomatic hypercalcemia; 10.III-IV and congestive heart failure (New York Heart Association classification), poorly controlled and clinically significant arrhythmias;
• Known allergic reactions to PD-1 monoclonal antibody, albumin paclitaxel, carboplatin active ingredients and/or any excipients;
• An active autoimmune disease requiring systemic treatment (e.g. with disease-modifying drugs, corticosteroids, or immunosuppressants) has occurred within 2 years prior to first administration. Replacement therapies (such as thyroxine, insulin, or physiological doses of corticosteroids for adrenal or pituitary insufficiency) are not considered systemic；
• Patients requiring long-term systemic use of corticosteroids. Patients with COPD or asthma requiring intermittent use of bronchodilators, inhaled corticosteroids, or local injections of corticosteroids could be enrolled；
• Wounds that have not healed for a long time or fractures that have not healed completely;
• Have an active infection requiring treatment or have used systemic anti-infective drugs within 1 week prior to first dosing;
• Arterial thrombotic events, such as cerebrovascular accidents (including transient ischemic attacks), myocardial infarction, and unstable angina pectoris, occurred within 6 months before screening;
• Known history of human immunodeficiency virus (HIV) infection (i.e., HIV1/2 antibody positive);
• Untreated active hepatitis B; Note: Hepatitis B subjects who meet the following criteria are also eligible for inclusion: HBV viral load must be < 1000 copies /ml (200IU/ml) prior to initial dosing, and subjects should receive anti-HBV therapy to avoid viral reactivation throughout the duration of study chemotherapy drug treatment. For subjects with anti-HBC (+), HBsAg (-), anti-HBS (-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring of viral reactivation is required.
• Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection)
• Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders;
• Have received live vaccine within 30 days prior to the first dose;Note: Injectable inactivated virus vaccine against seasonal influenza is permitted; However, live attenuated influenza vaccines administered intranasally are not permitted.
• There is a medical history, illness, treatment, or abnormal laboratory result that could interfere with the test results or prevent the subject from fully participating in the study, or the investigator believes that participation in the study is not in the subject's best interest.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• [1] Siegel RL, Miller KD, Jemal A: Cancer statistics, 20182018;68: 7-30. [2] 赫捷．2018 中国肿瘤登记年报［Ｍ］．北京：人民卫生出 版社，2019：129 [3] Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma [J]. N Engl J Med, 2007, 356(2): 115-124. [4] Escudier B, Szczylik C, Hutson T E, et al. Randomized phase II trial of first-line treatment with sorafenib versus interfero

Идентификаторы

NCT: NCT06574412 · 2024-HS-091

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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