Given the significant challenge of drug resistance in patients with advanced renal cell carcinoma (RCC) despite standard treatment, this study aims to translate preclinical findings into clinical practice, preliminarily evaluating the safety, tolerability, and preliminary efficacy of atorvastatin calcium combined with targeted and immunotherapy in patients with advanced RCC. We hypothesize that for some patients with advanced RCC who do not respond well to targeted + immunotherapy, identifying potential beneficiaries based on their PTC susceptibility testing and combining atorvastatin with these treatments in real-world settings could be an effective susceptibility enhancement strategy, thereby further improving patient survival. This prospective clinical study aims to validate the safety and efficacy of this "organoid-guided precision combination therapy model."
1\. Study Objectives 1.1 Primary Objective: To evaluate the effectiveness of personalized treatment strategies guided by patient-derived tumor cell cluster (PTC) susceptibility testing in patients with advanced/metastatic renal cell carcinoma. The primary endpoint is objective response rate (ORR). Specifically, this study compares the in vitro drug sensitivity differences between two treatment regimens: "targeted therapy + immunotherapy" and "targeted therapy + immunotherapy + atorvastatin calcium tablets," by performing PTC culture and susceptibility testing on tumor tissue obtained from patient biopsies. This will guide subsequent clinical treatment decisions regarding the addition of oral atorvastatin calcium tablets to standard targeted therapy combined with immunotherapy. 1.2 Secondary Objectives: 1. To evaluate the disease control rate, progression-free survival, overall survival, 12-month progression-free survival rate, and 12- and 24-month overall survival rates of atorvastatin combined with targeted and immunotherapy regimens in patients with advanced/metastatic renal cell carcinoma. 2. Safety: Incidence of adverse events and serious adverse reactions. 3. To evaluate health-related quality of life (HRQoL). 2\. Study Design 2.1 Overall Design This is a single-center, prospective, non-randomized controlled, two-arm clinical trial of superiority. The study plans to enroll 20-40 patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC). All subjects will receive targeted therapy plus immunotherapy. The addition of oral atorvastatin will be determined based on the drug sensitivity results of the patient-derived tumor cell cluster (PTC) model. Treatment will continue until any of the following occurs: disease progression, intolerable toxicity, the subject voluntarily requests to discontinue treatment or withdraw from the study, or other reasons determined by the investigator necessitate discontinuation of treatment and withdrawal from the study. This study consists of three phases: screening, treatment (visit), and follow-up. All subjects must meet the inclusion and exclusion criteria. The screening period will not exceed 28 days. After passing the screening examination and evaluation, subjects will enter the treatment period. The treatment period consists of 21-day cycles, during which subjects must receive treatment and undergo regular visits as specified in the protocol. Safety follow-up begins on day 30 (±7 days) from the start of the last study treatment, with participants required to undergo evaluation at the research center. Following the safety follow-up period, participants will enter a 2-year survival follow-up period, with follow-ups conducted at the end of every two treatment cycles. Follow-ups can be conducted via telephone or other effective methods, primarily collecting information on participant survival status and subsequent anti-tumor treatment. For participants without radiographic evidence of disease progression, imaging examinations will continue at the established efficacy assessment frequency until disease progression, death, loss to follow-up, withdrawal of informed consent, initiation of other anti-tumor treatments, or investigator termination of the study. 2.2 Study Endpoints 1. Primary endpoint: Objective response rate (ORR); 2. Secondary endpoints: Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), 12-month progression-free survival rate (PFS rate), 12-month overall survival rate (OS rate), 24-month overall survival rate (OS rate), safety, and health-related quality of life (HRQoL). 2.3 Study Location and Duration This study is planned to be conducted at a single center from April 2026 to April 2030, with the Cancer Hospital of the Chinese Academy of Medical Sciences as the main center. It is expected to enroll 20-40 patients with advanced or metastatic clear cell renal cell carcinoma. 2.4 Study Drugs 1. Axitinib (Inritar) Dosage Form: Tablets Strength: 5mg/tablet Dosage: Oral The initial dose is 5mg twice daily, and the dose can be gradually adjusted according to patient tolerance. 2. Toripalimab Injection (Tuoyi) Dosage Form: Injection Strength: 80mg/2ml Dosage: Intravenous Infusion Administer intravenously every 3 weeks at a dose of 240mg, continuously until disease progression or adverse reactions occur. 3. Atorvastatin Calcium Tablets (Lipitor) Dosage Form: Tablets Strength: 10mg/tablet Dosage: Oral The initial dose is 10mg once daily, which can be gradually adjusted according to patient tolerance. 2.5 PTC Construction Procedure This study used a patient-derived tumor cell cluster (PTC) model to assess drug sensitivity. The specific procedure included: 1. Collecting tumor tissue samples from patients with advanced renal cell carcinoma and culturing them in vitro in the laboratory. 2. Promoting the formation of tumor-like organoids by tumor cells under specific culture conditions, maintaining their biological characteristics in vitro. 3. Performing drug sensitivity testing to evaluate two drug combinations: targeted therapy combined with immunotherapy (axitinib + toripalimab) or targeted therapy combined with immunotherapy and atorvastatin calcium tablets (axitinib + toripalimab + atorvastatin). 4. Evaluating the inhibitory effect of different drug combinations on tumor cells in the PTC model by exposing them to different drug combinations, and deciding whether to provide combination therapy to patients based on the drug sensitivity results.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Axitinib 5 mg orally twice daily.
Toripalimab 240 mg intravenously every 3 weeks.
Atorvastatin calcium 10 mg orally once daily, administered based on patient-derived tumor-like cell cluster drug sensitivity testing.
Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, Beijing 101205
Beijing, Chaoyang District, China
Objective Response Rate (ORR)
ORR is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) according to RECIST version 1.1.
Time frame: From baseline until disease progression, death, withdrawal, or end of treatment, assessed up to 24 months.
Progression-Free Survival (PFS)
PFS is defined as the time from treatment initiation to disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.
Time frame: From treatment initiation until disease progression or death, assessed up to 24 months.
Overall Survival (OS)
OS is defined as the time from treatment initiation to death from any cause.
Time frame: From treatment initiation until death from any cause, assessed up to 48 months.
Disease Control Rate (DCR)
DCR is defined as the proportion of participants who achieve complete response, partial response, or stable disease according to RECIST version 1.1.
Time frame: From baseline until disease progression, assessed up to 24 months.
12-Month Progression-Free Survival Rate
The proportion of participants who remain alive without disease progression at 12 months after treatment initiation.
Time frame: 12 months after treatment initiation.
12-Month Overall Survival Rate
The proportion of participants who remain alive at 12 months after treatment initiation.
Time frame: 12 months after treatment initiation.
24-Month Overall Survival Rate
The proportion of participants who remain alive at 24 months after treatment initiation.
Time frame: 24 months after treatment initiation.
Incidence of Adverse Events
Safety will be assessed by the incidence and severity of adverse events and serious adverse events graded according to NCI-CTCAE version 5.0.
Time frame: From treatment initiation to 30 days after the last dose of study treatment.
Health-Related Quality of Life (HRQoL)
HRQoL will be assessed using the EORTC QLQ-C30 questionnaire.
Time frame: From baseline through treatment and follow-up, assessed up to 24 months.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.