Preoperative Therapy of Super-selective Tumor Artery Embolization Combined With Toripalimab and Axitinib in Advanced RCC

Официальное название

A Study on the Safety and Efficacy of Super-selective Tumour Arterial Embolisation in Combination With Toripalimab and Axitinib as a Preoperative Treatment for Advanced Renal Cell Carcinoma

Обзор

This is a phase II study to determine the efficacy and safety of Super-selective tumor artery embolization combined with toripalimab and axitinib as treatment for patients with the advanced kidney cancer . Further evaluate whether the treatment plan is beneficial to the patient's operation. Patients will undergo super-selective embolization of the feeding arteries to the renal tumour one week prior to drug therapy, followed by toripalimab administered every three weeks for three to four consecutive cycles combined with axitinib administered for four consecutive cycles in the preoperative and patients need to continue taking the drug for a year after surgery

Подробное описание

This is a phase II study to determine the efficacy and safety of Super-selective tumor artery embolization combined with toripalimab and axitinib as treatment for patients with the advanced kidney cancer . Further evaluate whether the treatment plan is beneficial to the patient's operation. Patients will undergo super-selective embolization of the feeding arteries to the renal tumour one week prior to drug therapy, followed by toripalimab administered every three weeks for three to four consecutive cycles combined with axitinib administered for four consecutive cycles in the preoperative and patients need to continue taking the drug for a year after surgery, The main objective of the study was to evaluate whether the treatment was beneficial to patients undergoing surgery.

Вмешательства

• Препарат Toripalimab and axitinib
  Patients will undergo super-selective embolization of the feeding arteries to the renal tumour one week prior to drug therapy, followed by toripalimab administered every three weeks for four consecutive cycles combined with axitinib administered for four consecutive cycles before surgery, and followed by 17 cycles' toripalimab for adjuvant therapy.

Первичные конечные точки

• R0 Resection Rate [Срок оценки: through study completion, an average of 3 year]
• ORR [Срок оценки: through study completion, an average of 3 year]
• Preoperative Treatment Safety: Treatment-Related Side Effects [Срок оценки: Through treatment completion (before surgery), an average of 4 cycles (each cycle is 21 days)]

Вторичные конечные точки (5)

• Perioperative Complications [Срок оценки: Throughout treatment until 30 days after surgery]
• Progression free survival [Срок оценки: Every 12 weeks until 12 months after surgery]
• Major Pathological Response [Срок оценки: Within 14 days after surgical resection]
• Patient-Reported Quality of Life [Срок оценки: Through adjuvant treatment completion (after surgery), with assessments once every 3 weeks for a total of 17 cycles (each cycle is 21 days)]
• Overall Survival (OS) [Срок оценки: Follow-up is performed once every 3 months (±14 days)]

Критерии участия

Критерии включения

• Willing and able to provide written informed consent
• Age ≥ 18 years
• Patients with pathologically and radiographically confirmed renal cell carcinoma:

• cT2N0M0 with Grade 4 or sarcomatoid feature;
• cT3-4N0M0;
• cTanyN1M0;
• M1 that can be returned to M0 through local therapy
• Preoperative imaging evaluation can be performed radical excision or tumor reduction surgery
• There are no suspected brain metastases
• The presence of measurable lesions was assessed according to RECISTv1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Organ function level must meet the following requirements: Hematological indexes: neutrophil count >= 1.5x10\^9/L, platelet count >= 100x10\^9/L, hemoglobin >= 9.0 g/dl (can be maintained by blood transfusion); Liver function: total bilirubin <=1.5 ULN, alanine aminotransferase and aspartate aminotransferase <=1.5 ULN
• Non-surgically sterilized or reproductive-age female patients must use a medically approved contraceptive method (such as an intrauterine device, oral contraceptives, or condoms) during the study treatment period and for 3 months after its completion; Female patients who are not surgically sterilized or are of childbearing potential must have a negative serum or urine HCG test within 7 days prior to study enrollment and must not be lactating. Male patients who are not surgically sterilized or are of childbearing potential must agree to use one medically approved contraceptive method with their spouse during the study treatment period and for 3 months after the study treatment period ends.
• The subjects volunteered to join the study, signed informed consent, and had good compliance with follow-up

Критерии исключения

• Prior receipt of radiotherapy, chemotherapy, long-term or high-dose corticosteroid therapy, surgery, or molecular targeted therapy
• Subjects with a history of or concurrent other malignancies (except those controllable and not affecting 2-year survival)
• Prior treatment with other PD-1/PD-L1 therapies; Known history of allergy to macromolecular protein preparations or any known PD-1 component
• Active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Subjects with vitiligo or childhood asthma that has achieved complete remission without requiring any intervention in adulthood may be included; subjects requiring medical intervention with bronchodilators for asthma are excluded);
• Subjects currently using immunosuppressive agents for immunosuppression purposes and continuing such use within 2 weeks prior to enrollment
• Uncontrolled cardiac clinical symptoms or diseases, such as:

• New York Heart Association (NYHA) Class II or higher heart failure;
• Unstable angina;
• Myocardial infarction within the past year;
• Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention
• Coagulation abnormalities (PT > 16s, APTT > 43s, TT > 21s, Fbg > 2g/L) with bleeding tendency or currently receiving thrombolytic or anticoagulant therapy;
• Active gastrointestinal bleeding within 3 months prior to first dose due to esophageal varices, active gastric or duodenal ulcer, ulcerative colitis, portal hypertension, or unresected tumors; or other conditions judged by the investigator to potentially cause gastrointestinal bleeding or perforation
• History or current presence of major bleeding (≥30 mL within 3 months), hemoptysis (≥5 mL fresh blood within 4 weeks), or thromboembolic events (including stroke and/or transient ischemic attack) within 12 months
• Active infection or unexplained fever >38.5°C occurring during screening or prior to first dose
• History of abdominal fistula, gastrointestinal perforation, or abdominal abscess within 4 weeks prior to first dose
• Objective evidence of past or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or severe pulmonary impairment
• Subjects with congenital or acquired immunodeficiency, such as HIV infection, or active hepatitis (transaminase levels not meeting inclusion criteria; for hepatitis B: HBV DNA ≥10⁴/ml; for hepatitis C: HCV RNA ≥10³/ml); chronic hepatitis B virus carriers with HBV DNA ≥2000 IU/ml (≥10⁴ copies/ml) must concurrently receive antiviral therapy during the study to be eligible for enrollment
• Subjects currently participating in other clinical studies or those who completed a prior clinical study within the past month; subjects may receive other systemic antitumor therapies during the study period
• Administration of live vaccines within 4 weeks prior to study drug initiation or during the study period
• Known history of psychiatric drug abuse, alcoholism, or substance abuse;
• Inability or refusal to bear out-of-pocket costs for examinations and treatments
• The investigator deems the subject should be excluded from this study, such as when the investigator determines the subject has other factors that may necessitate premature termination of the study, including: other serious illnesses (including psychiatric disorders) requiring concomitant treatment, severe laboratory abnormalities, or family/social factors that may compromise subject safety or interfere with data/sample collection.

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

Китай · 1 центр

• Tianjin Medical University Second Hospital — Тяньцзинь

Публикации

• ournal/Source：Presented at: American Society of Clinical Oncology - Genitourinary Cancers Symposium (ASCO - GU) 2025 • Publication Year：2025 • Other Info：Abstract #477684
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• EuroQol Group. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990 Dec;16(3):199-208. doi: 10.1016/0168-8510(90)90421-9. PMID 10109801
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• Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. doi: 10.1056/NEJMoa1303989. PMID 23964934
• Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators. Ni PMID 29562145
• Zhang Z, Xiong L, Wu Z, Liu H, Ning K, Peng Y, Yu C, Ding Y, Weng D, Xia J, Jiang L, Guo S, Han H, Zhou F, Dong P. Neoadjuvant combination of pazopanib or axitinib and programmed cell death protein-1-activated dendritic cell-cytokine-induced killer cells immunotherapy may facilitate surgery in patients with renal cell carcinoma. Transl Androl Urol. 2021 May;10(5):2091-2102. doi: 10.21037/tau-21-40 PMID 34159090

Идентификаторы

NCT: NCT07172386 · SETAR

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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