Solid Tumor
Conditions
Interventions
Mild Cold Exposure Plus Standard PD-1/PD-L1 Therapy Arm:Standard PD-1/PD-L1 inhibitor monotherapy or standard combination regimens containing PD-1/PD-L1 inhibitors
Controlled mild cold exposure at 18°C
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Participants are aged 18–75 years, of either sex, with an expected survival of at least 3 months. 2. Patients must have histologically or cytologically confirmed solid malignant tumors (including, but not limited to, lung cancer, breast cancer, gastrointestinal tumors, and genitourinary tumors), with at least one measurable or evaluable lesion according to RECIST version 1.1. 3. Patients may be treatment-naïve or previously treated with radiotherapy, chemotherapy, targeted therapy, or immunotherapy (including PD-1/PD-L1 inhibitors), provided that no severe unresolved treatment-related toxicities are present at the initiation of the study treatment; for those previously treated with immune checkpoint inhibitors, a washout period of at least 4 weeks is required prior to enrollment, and any related adverse events must have resolved to Grade =1. 4. Patients receiving systemic corticosteroids at physiologic doses are eligible, provided the dose does not exceed a predefined acceptable threshold. 5. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1; selected patients with ECOG 2 may be considered at the investigator’s discretion if deemed able to tolerate the study intervention, and all participants must be capable of self-care in daily life. 6. Adequate organ function is required, including hematologic parameters (absolute neutrophil count =1.5 × 10?/L, platelet count =100 × 10?/L, hemoglobin =90 g/L), hepatic function (total bilirubin =1.5 × upper limit of normal [ULN], AST/ALT =2.5 × ULN or =5 × ULN in the presence of liver metastases), renal function (serum creatinine =1.5 × ULN or creatinine clearance =50 mL/min), and no uncontrolled abnormalities in thyroid function or fasting blood glucose (patients with type 2 diabetes are allowed if well controlled). 7. Participants must have adequate cardiopulmonary function, including no symptomatic myocardial ischemia or severe arrhythmia, resting oxygen saturation >92%, no acute exacerbation of severe chronic respiratory disease, and cardiac function classified as New York Heart Association (NYHA) class I–II. 8. Participants must have no contraindications to cold exposure, including absence of severe Raynaud’s phenomenon, cold urticaria, cryoglobulinemia, or other cold-sensitive disorders, and no severe cardiovascular diseases (e.g., recent myocardial infarction, uncontrolled hypertension, or angina) that could be exacerbated by cold exposure. 9. Female participants must not be pregnant or breastfeeding and must agree to use effective contraception during the study and for at least 3 months after the last dose; male participants must also agree to use effective contraception during the study and for at least 3 months after the last dose; women of childbearing potential must have a negative pregnancy test prior to enrollment. 10. Participants must be able to understand the study procedures, voluntarily provide written informed consent, and be willing to comply with all protocol-specified assessments and follow-up.
Exclusion criteria
Exclusion criteria: 1. Participants who are currently receiving, or have received within 4 weeks prior to the initiation of study treatment, another investigational drug or are participating in another clinical study. 2. Presence of any uncontrolled active infection, including severe bacterial, viral, or fungal infections, such as active tuberculosis, or known HIV infection; patients with chronic hepatitis B or hepatitis C infection may be eligible if viral load is adequately controlled (e.g., HBV DNA below a predefined threshold) and liver function meets the inclusion criteria; otherwise, they will be excluded. 3. Known hypersensitivity or allergy to any medications that may be used during the study. 4. Active autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis) or a history of autoimmune disease requiring long-term immunosuppressive therapy; patients with a history of immune-related adverse events (irAEs) leading to discontinuation of PD-1 therapy should be carefully evaluated; any unresolved toxicity from prior treatment of Grade >=3 immune-related adverse events according to CTCAE version 5.0 will lead to exclusion. 5. History of severe adverse events (e.g., hepatitis, pneumonitis, colitis, or severe endocrine disorders of Grade >=3) during prior PD-1/PD-L1 inhibitor therapy that have not fully resolved or are considered to have a high risk of recurrence upon re-exposure. 6. Significant cardiovascular disease, including but not limited to unstable angina, clinically significant arrhythmias requiring treatment, congestive heart failure (New York Heart Association [NYHA] class III–IV), or left ventricular ejection fraction 13.9 mmol/L) that may be exacerbated by cold exposure, severe chronic obstructive pulmonary disease or asthma prone to acute exacerbations in cold environments, or generally poor physical condition rendering the patient unable to tolerate potential risks.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Feasibility; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate, ORR;Progression-Free Survival, PFS;Overall Survival, OS;Brown Adipose Tissue Activation;Peripheral Immune Profile and Circulating Cytokine Changes;Metabolomic Changes;Gut Microbiota Changes;Patient-Reported Outcomes;Changes in Immune- and Metabolism-Related Tumor Tissue Biomarkers;Disease Control Rate, DCR;Pathological Response Rate;R0 Resection Rate; | — |
Countries
China
Contacts
Public ContactXuelei Ma
West China Hospital, Sichuan University
Outcome results
None listed