Melanoma
Conditions
Brief summary
The study was a single-arm study designed to evaluate the efficacy and safety of Chidamide combined with Toripalimab.
Interventions
DRUGChidamide combined with Toripalimab
chidamide：oral, 30 mg/time, twice weekly; Toripalimab：intravenous drip, 240mg, once every 3 weeks
Sponsors
Peking University Cancer Hospital & Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* aged ≥ 18 years, male or female * histologically and/or cytologically confirmed melanoma, clinically diagnosed as inoperable stage III-IV * previous treatment for advanced tumors (including chemotherapy, targeted, anti-vascular drugs, etc.) failure or no standard treatment, and no PD- (L) 1/CTLA-4 drug treatment; if neoadjuvant/adjuvant therapy has received PD- (L) 1/CTLA-4 drug treatment, the total duration of drug treatment should be ≥6 months * if there is brain metastasis, local treatment must have been received before participating in this study and clinical stability ≥ 3 months * ECOG score 0-1 * at least one measurable lesion (according to RECISTv1.1 evaluation criteria) * absolute neutrophil count ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 90 g/L * other organ function needs to meet: ① cardiac function needs to meet: left ventricular ejection fraction ≥ 50%, no organic arrhythmia; ② liver function needs to meet: ALT and AST ≤ 2.5 times the upper limit of normal (such as with liver metastasis, ALT and AST ≤ 5 times the upper limit of normal), total bilirubin ≤ 1.5 times the upper limit of normal;③ renal function needs to meet: creatinine ≤ 1.5 times the upper limit of normal; ④ coagulation function: international normalized ratio (International Normalized Ratio,INR) ≤ 1.5 times upper limit of normal; prothrombin time (PT), activated partial thromboplastin time (APTT) ≤ 1.5 times upper limit of normal (unless the subject was receiving anticoagulant therapy and PT and APTT were within the expected range of anticoagulant therapy at screening); ⑤ Thyroid function: thyrotropin (TSH) or free thyroxine (FT4) or free triiodothyronine (FT3) were within ± 10% of normal values. * Expected survival time ≥ 3 months * Voluntarily participate in this clinical trial and sign a written informed consent. * Previous anti-tumor therapy (chemotherapy, radiotherapy, targeting, traditional Chinese medicine, other immunotherapy) requires eluting for 28 days. * The adverse effects of previous antitumor therapy were resolved to grade 0-1 before the screening period (as determined by NCI CTCAE 5.0; Except for toxicity, such as hair loss, which the investigator determined did not pose a safety risk to the subject)
Exclusion criteria
* no measurable lesions, such as pleural or pericardial exudates, ascites, etc. * choroidal melanoma * previous treatment with HDAC inhibitors (including cedaramide, romidepsin, vorinostat, bellistat, panobinostat, etc.) * history of interstitial lung disease or pneumonia requiring oral or intravenous steroids * previous vaccination or planned vaccination with live vaccines (seasonal influenza vaccine without live vaccines is allowed), major surgery within 30 days before the first study treatment * active infection \[active bacterial, viral, fungal, mycobacterial, parasitic infections or other infections (excluding fungal infections of the nail bed) within 4 weeks before the screening period, or any major infection event requiring intravenous antibiotic therapy, or targeted antiviral therapy, or hospitalization; Active hepatitis is defined as HBsAg positive with HBV DNA≥500 IU/ml or HCV antibody positive with HCV copy number \> the upper limit of normal\], or persistent fever within 14 days before screening * history of immunodeficiency, including positive HIV testing, or other acquired, congenital immunodeficiency diseases, or history of organ transplantation * uncontrolled cardiovascular disease; history of clinically significant QT prolongation, or screening period \> 470 ms for females and \> 450 ms for males * positive baseline pregnancy test in female subjects who are pregnant or lactating or fertile females; or subjects of childbearing age who are unwilling to take effective contraceptive measures for at least 180 days during study participation and after the last dose of study drug * According to the investigator 's judgment, there are concomitant diseases that seriously jeopardize the subject' s safety or affect the subject 's completion of the study (e.g., severe hypertension ≥ 180/110 mmHg, uncontrolled diabetes, thyroid disease, Hypertriglyceridemia ≥ grade 2, etc.) * History of definite neurological or psychiatric disorders, including epilepsy or dementia * Any condition that, in the opinion of the investigator, would make participation in this study inappropriate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to approximately 24 months | Objective response rate (ORR)as measure of efficacy by RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free survival （PFS） | Up to approximately 24 months | Defined as the time from first dosing (C1D1) to date of first observed progression or death from any cause (whichever comes first) |
| Overall Survival（OS） | Up to approximately 24 months | OS as measure of efficacy by RECIST 1.1 |
| Duration of Response(DoR) | Up to approximately 24 months | DoR as measure of efficacy by RECIST 1.1 |
| Disease control rate（DCR） | Up to approximately 24 months | Defined as the percentage of patients who have achieved a confirmed response of at least CR or PR or a response of SD |
| Incidence Rate of each Toxicity (safety and tolerability) | Up to approximately 24 months | safety and tolerability as measure of efficacy by CTCAE 5.0 |
Countries
China
Contacts
Primary ContactJun Guo, Doctor
Outcome results
None listed