melanoma
Conditions
Interventions
experimental group:retinoic acid capsules plus toripalimab
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 90 Years
Inclusion criteria
Inclusion criteria: 1. Patients voluntarily join this study and sign an informed consent form; 2. Age = 18, both males and females are eligible; 3. Histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) cutaneous/acral melanoma, with at least one measurable lesion per RECIST criteria on imaging studies (CT or MRI); 4. Untreated advanced or metastatic diseases, except for those that have previously received targeted therapy or immunotherapy (such as anti-CTLA-4, anti-PD-1 therapy) as adjuvant therapy or neoadjuvant therapy; It is only allowed if there is no recurrence during immunotherapy or within 6 months after treatment termination; No other previous or neoadjuvant treatments are allowed; 5. Not receiving radiation therapy; 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 7. Expected survival period = 12 weeks; 8. Provide tumor biopsy sufficient for whole exome sequencing, RNA seq, and methylation sequencing studies; 9. Patient must have adequate organ function as indicated by the following laboratory values: (1) Absolute neutrophil count = 1.5 × 10^9/L; (2) Platelets = 80 × 10^9/L; Hemoglobin = 90 g/L; (3) Serum albumin = 30g/L; (4) Thyroid stimulating hormone (TSH) = 1 × ULN (if abnormal, FT3 and FT4 levels should be examined simultaneously. If FT3 and FT4 levels are normal, they can be included in the group); (5) Bilirubin = 1.5 × ULN (within 7 days before first use); (6) ALT and AST = 2.5 × ULN (within 7 days before first use) or = 5 × ULN (for patients with liver metastasis); (7) AKP= 1.5×ULN; (8) Serum creatinine = 1.5 × ULN; 10. Non surgical sterilization or female patients of childbearing age are required to use a medically approved contraceptive measure (such as intrauterine device, contraceptive pill, or condom) during the study treatment period and within 6 months after the end of the study treatment period; Female patients of childbearing age who undergo non-surgical sterilization must have a negative serum or urine HCG test within 72 hours prior to enrollment in the study; And it must be during non lactation period; For male patients whose partners are women of childbearing age, effective contraception methods should be used during the trial period and within 6 months after the last dose.
Exclusion criteria
Exclusion criteria: 1. Patients with any active autoimmune diseases or a history of autoimmune diseases (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism; patients with vitiligo; asthma that has been completely relieved in childhood and does not require any intervention in adulthood can be included; asthma that requires medical intervention with bronchodilators cannot be included); 2. The patient is currently using immunosuppressants or systemic corticosteroid therapy to achieve immunosuppression (dose>10mg/day of prednison or other therapeutic corticosteroids), and has continued to use them within the 2 weeks prior to enrollment; 3. The patient has a history of malignant tumors within 5 years prior to the first study administration (excluding the diseases being treated in this study). It does not include adequate treatment of stage 1 or stage 2 skin basal/squamous cell carcinoma, cervical carcinoma or breast cancer in situ, or other carcinoma in situ; 4. Has an active infection requiring systemic therapy; 5. Has experienced severe allergic reactions to other monoclonal antibodies; 6. Has known sensitivity to retinoic acid derivatives; 7. Clinical symptoms or diseases of the heart that have not been well controlled, such as NYHA grade 2 or above heart failure; Unstable angina pectoris; Have experienced myocardial infarction within one year; Clinically significant supraventricular or ventricular arrhythmias require treatment or intervention; QTc interval prolonged to>480msec; 8. Abnormal coagulation function (INR>2.0, PT>16s), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy, prophylactic use of low-dose aspirin and low molecular weight heparin is allowed; 9. Within the first 3 months of enrollment, there have been significant clinical bleeding symptoms or clear bleeding tendencies, such as coughing/hemoptysis of 2.5ml or more per day, lower gastrointestinal bleeding, esophageal and gastric varices at risk of bleeding, hemorrhagic gastric ulcers, or vasculitis; 10. Arterial/venous thrombotic events that occurred within the first 6 months of enrollment, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; 11. Known genetic or acquired bleeding and thrombophilia tendencies (such as hemophilia patients, coagulation dysfunction, thrombocytopenia, etc.); 12. Suffering from hypertension and unable to achieve good control with antihypertensive medication (systolic blood pressure = 140mmHg or diastolic blood pressure = 90mmHg); 13. Urine routine shows that urine protein is =++and it has been confirmed that the 24-hour urine protein level is>1.0g; 14. Patients who have previously received radiation therapy, chemotherapy, hormone therapy, or surgery and have completed treatment (last medication) less than 4 weeks before the study medication; Patients undergoing molecular targeted therapy (including other oral targeted drugs used in clinical trials) with less than 5 half-life from the first study dose, or adverse events caused by previous treatment (excluding hair loss) that have not recovered to = CTCAE grade 1; 15. Eye melanoma, mucosal melanoma, primary unknown melanoma; 16. Patients with severe local invasion of the lesion and a risk of organ leakage, massive bleeding, or perforation; 17. Pregnant o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival;Overall survival;Time to objective response;Duration of response;Incidence of skin adverse reactions;Exploratory biomarker analysis; | — |
Countries
China
Contacts
Public ContactYong Chen
Fudan University Shanghai Cancer Center
Outcome results
None listed