Clinical trial NCT05478473: Clinical Study of Chidamide Combined With Toripalimab in the Treatment of Advanced Melanoma
Official title: Clinical Study of Chidamide Combined With Toripalimab in the Treatment of Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Melanoma
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2022-07-28
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study was a single-arm study designed to evaluate the efficacy and safety of Chidamide combined with Toripalimab.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Progression Free survival （PFS）
timeFrame: Up to approximately 24 months
measure: Overall Survival（OS）
timeFrame: Up to approximately 24 months
measure: Duration of Response(DoR)
timeFrame: Up to approximately 24 months
measure: Disease control rate（DCR）
timeFrame: Up to approximately 24 months
measure: Incidence Rate of each Toxicity (safety and tolerability)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
References: