Advanced Breast Cancer
Conditions
Interventions
Experimental group:TIL cells were infused back
Sponsors
The Affiliated Hospital of Qingdao University
Eligibility
Sex/Gender
Female
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18-75 years (including the critical value); 2. Clinically diagnosed patients with advanced advanced breast cancer (female); 3. Progression of disease after at least one standard treatment; There is no effective treatment available or other treatments are refused (refer to the latest version of Diagnosis and treatment guidelines for each cancer for ''effective treatment''); 4. There is at least one resectable tumor lesion that has not received radiotherapy or other local therapy within 28 days, from which at least a 1cm^3 volume of tissue can be isolated, or a sufficient TIL can be prepared (either from a single lesion or from a combination of multiple lesions); If no lesions can be resected, a tumor sample of similar size should be obtained by puncture or bronchoscopy for the preparation of autologous tumor infiltrating lymphocytes (minimally invasive treatment as possible); 5. At least one measurable lesion, as defined by RECIST 1.1, that has not received radiotherapy or other local therapy (unless such therapy occurred earlier than 28 days and the lesion has shown substantial progression); 6. ECOG =3 months; 8. There was adequate organ and bone marrow function at the assessment within the 7-day (+ 3-day window) initial screening, as defined below: (1) Blood routine: neutrophil count >=1.5x10^9/L, platelet count >=90x10^9/L, hemoglobin >=90g/L (no blood transfusion or erythropoietin treatment within 14 days); (2) Liver function: ALT and AST levels =45mL/min (Cockcroft-Gault formula); (4) Coagulation function: activated partial thromboplastin time (APTT) 50% by color ultrasound; Asymptomatic or poorly controlled arrhythmia; QT interval was not prolonged, QTc60% or FEV1/FVC>0.7, and percutaneous oxygen saturation >=92% at rest; 9. Prior to tumor sampling, adverse reactions caused by previous treatment had recovered to CTCAE 5.0 <=1 (except for toxicity without safety risk as determined by researchers, such as hair loss); 10. Patients who have agreed to take effective non-drug contraception within 180 days from signing the informed consent to the end of the study; 11. Those who fully understand the test and voluntarily sign the informed consent.
Exclusion criteria
Exclusion criteria: 1. Known severe allergic reactions (>= grade 3) to test related drugs (cyclophosphamide, fludarabine, interleukin-2) and their active ingredients and/or any excipients; 2. Have any uncontrollable clinical problems, including but not limited to: (1) Hypertension with poor drug control (blood pressure >=150/90mmHg in quiet state after medication); (2) Poorly controlled diabetes mellitus; (3) Heart disease (Class III/IV congestive heart failure or heart block as defined by the New York Heart Association); 3. The following cases occurred in the 6 months before screening: Deep vein thrombosis or pulmonary embolism; Myocardial infarction; Severe or unstable arrhythmia or angina; Percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; Cerebrovascular accident, transient ischemic attack, cerebral embolism; 4. Active autoimmune diseases requiring systemic treatment during the study period or organ transplant recipients, or a history of such diseases within the past 2 years; 5. Any immunosuppressive drugs, such as corticosteroids, were used within 14 days prior to enrollment. Physiological doses of glucocorticoids (<=10 mg/ day of prednisone or equivalent) are permitted; Inhaled, intranasal, or topical corticosteroids are permitted; 6. Symptomatic brain metastases. Patients with asymptomatic BMS or stable symptoms after treatment of BMS were eligible to participate in this study if they met all of the following criteria: (1) Measurable lesions outside the central nervous system, allowing treatment of BMS with radiation or surgery; (2) The maximum lesion diameter <= 1cm and the number of lesions <= 3 cases; (3) No meningeal, midbrain, pontine, bulbar or spinal metastasis; (4) The clinical stable state was maintained for at least 4 weeks before enrollment; 7. TIL anticancer therapy used before collection: chemotherapy, immune checkpoint inhibitors, other investigational drug therapy, or topical therapy to target lesions within the last 4 weeks; Received systemic systemic therapy with Chinese patent drugs with anti-tumor indications or immunomodulatory drugs (including thymosin and interferon) in the past 2 weeks; Received targeted drugs in the past 4 weeks (If the target drug metabolizes with 5 half-lives less than 4 weeks, 5 half-lives shall prevail); 8. Acute or chronic infections are present, including: (1) A known history of testing positive for human immunodeficiency virus (HIV) or a known history of acquired immunodeficiency syndrome; (2) Active tuberculosis infection (based on clinical symptoms, physical examination and/or imaging, and laboratory findings); (3) There is an active bacterial or fungal infection requiring systemic treatment; (4) Hepatitis B surface antigen, hepatitis B e antigen, hepatitis B e antibody and hepatitis B core antibody positive patients; (5) Hepatitis C patients; (6) Patients with positive antibody to treponema pallidum; 9. Patients who have received the novel coronavirus vaccine within 14 days prior to screening or have received live vaccine within 3 months prior to screening or plan to receive live vaccine during the trial; 10. Had major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to screening, or required elective surgery during the trial period; 11. Other malignancies diagnosed within 5 years prior to screening, excluding radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or radical
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerance; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate;Disease control rate;Time-to-response;Duration of response;Overall survival; | — |
Countries
China
Contacts
Public ContactWang Haibo, Cao Yu
Outcome results
None listed