Sebaceous Gland Carcinoma
Conditions
Brief summary
The goal of this clinical trial is to evaluate the efficacy and safety of neoadjuvant therapy with Sintilimab combined with Disitamab Vedotin in patients with locally advanced, resectable or potentially resectable sebaceous gland carcinoma. The main questions it aims to answer are: What is the major pathological response (MPR) rate after the neoadjuvant therapy? What are the pathological complete response (pCR) rate, clinical objective response rate (ORR), disease control rate (DCR), safety profiles, and 1-year disease-free survival (DFS) of this regimen? Participants will:Receive neoadjuvant therapy consisting of Sintilimab (200 mg, IV, Day 1) and Disitamab Vedotin (2.5 mg/kg, IV, Day 1) every 3 weeks for a total of 2 cycles. Undergo radical surgery after the completion of the neoadjuvant treatment phase. Receive postoperative adjuvant therapy after surgery, which includes uniform Sintilimab monotherapy maintenance (200 mg, IV, Q3W) for up to 1 year, and may receive risk-stratified local interventions (such as local radiotherapy or repeat wide excision) depending on the pathological risk factors.
Interventions
DRUGSintilimab
Sintilimab is administered at 200 mg intravenously on Day 1 of each 3-week cycle. In the neoadjuvant phase, it is given concurrently with Disitamab Vedotin for 2 cycles before radical surgery. In the adjuvant phase, post-surgery, it is administered as monotherapy maintenance for up to 1 year, or until intolerable toxicity or distant disease progression occurs.
DRUGdisitamab vedotin
Disitamab Vedotin is administered at 2.5 mg/kg intravenously on Day 1 of each 3-week cycle. It is given exclusively during the neoadjuvant phase for a total of 2 cycles concurrently with Sintilimab prior to radical surgery.
Sponsors
West China Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1.Age 18 to 85 years (inclusive), regardless of gender; 2.Pathologically confirmed sebaceous gland carcinoma of the eyelid meeting the following criteria: a) Locally advanced disease; b) Deemed resectable or potentially resectable based on ophthalmic evaluation; c) Willing to undergo surgical treatment; 3.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; 4. Adequate organ and bone marrow functions defined as follows: a) Hematology: Absolute neutrophil count (NEUT#) ≥ 1.5 × 10\^9/L; Platelet count (PLT) ≥ 80 × 10\^9/L; Hemoglobin ≥ 8 g/dL; b) Hepatic function: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × upper limit of normal (ULN); Total bilirubin (TBIL) ≤ 1.5 × ULN; c) Serum albumin ≥ 2.8 g/dL; d) Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance rate (CCR) \> 60 mL/min; e) Coagulation function: International Normalized Ratio (INR) ≤ 1.5; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 5. Volunteer to participate in the study, provide written informed consent, and be capable of complying with all protocol-specified visits and related procedures
Exclusion criteria
Participants meeting any of the following criteria will be excluded: 1) History of other malignancies, except for cured skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, and gastrointestinal intramucosal carcinoma with no recurrence within 5 years, or other malignancies deemed eligible by the investigator; 2) Any active autoimmune disease or history of autoimmune disease; 3) History of allergic diseases, severe drug allergies, or any component of the prescription (Note: severe allergy refers to those resulting in hospitalization); 4) Received any of the following treatments: a) Prior treatment with anti-PD-1, anti-PD-L1, or anti-HER2 therapies; b) Prior vaccination with anti-tumor vaccines; c) Use of any live vaccines against infectious diseases (such as influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to the first dose or planned during the study period; d) Major surgery or severe trauma within 4 weeks prior to the first dose; 5) Concomitant severe medical conditions; 6) Known history of interstitial lung disease (ILD), non-infectious pneumonitis, or high suspicion of ILD, or subjects who may interfere with the detection or management of suspected drug-related pulmonary toxicity (subjects with a history of drug-induced or radiation-induced asymptomatic non-infectious pneumonitis are allowed to be enrolled), active tuberculosis, or a history of tuberculosis infection that remains uncontrolled after treatment; 7) Patients with hyperthyroidism and patients with organic thyroid diseases cannot be enrolled, patients with hypothyroidism on a stable dose of thyroid hormone replacement therapy can be enrolled, and patients with hypothyroidism controlled by thyroid hormone replacement therapy can be enrolled (whether it is controlled shall be confirmed by the investigator and/or the endocrinology department); 8) Active infection, or unexplained fever occurring during screening or within 48 hours prior to the first dose, or use of systemic antibiotics within 1 week prior to signing the informed consent form; 9) Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL) or hepatitis C (HCV antibody positive and HCV RNA above the lower limit of detection of the assay), or a known history of positive human immunodeficiency virus (HIV) test, or known acquired immunodeficiency syndrome (AIDS); 10) Clear prior history of neurological or psychiatric disorders, such as epilepsy or dementia; 11) Clear history of drug abuse or history of alcohol abuse within 3 months; 12) Pregnant or lactating women, subjects (and their partners) who have reproductive plans, engage in unprotected sexual intercourse, or are unwilling to adopt appropriate contraceptive methods (such as condoms, intrauterine devices, or partner ligation) from the screening period up to 3 months after the end of the study; 13) Received any investigational drug within 4 weeks prior to the first use of the study drug, or concurrently enrolled in another clinical study, unless it is an observational (non-interventional) clinical study or follow-up phase of an interventional clinical study; 14) Other factors deemed by the investigator that may affect the study, leading to the inability to complete study treatment and follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathologic Response (MPR) Rate | At the time of surgery, after completion of neoadjuvant treatment | Among participants who undergo surgery, major pathologic response (MPR) is defined according to immune-related pathologic response criteria (irPRC) as ≤10% residual viable tumor cells in the tumor bed (%RVT ≤10%), regardless of whether residual viable tumor cells are present in lymph nodes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) Rate | At the time of surgery, after completion of neoadjuvant treatment | Among participants who undergo surgery, pathologic complete response (pCR) is defined according to immune-related pathologic response criteria (irPR) as no residual viable tumor cells in the tumor bed or resected lymph nodes (%RVT = 0). |
| Objective Response Rate (ORR) | From baseline to pre-operative tumor assessment following 2 cycles of neoadjuvant therapy (up to 9 weeks) | Objective response rate (ORR) is defined as the proportion of participants with a complete response (CR) or partial response (PR), as assessed according to RECIST version 1.1 |
| Disease Control Rate (DCR) | From baseline to pre-operative tumor assessment following 2 cycles of neoadjuvant therapy (up to 9 weeks). | Disease control rate (DCR) is defined as the proportion of participants with a complete response (CR), partial response (PR), or stable disease (SD), as assessed according to RECIST version 1.1 |
| Adverse Events (AEs) | From first dose through 30 days after the last dose of neoadjuvant treatment | Adverse events (AEs) will be assessed according to CTCAE version 5.0, and all treatment-related adverse events will be reported to evaluate the safety of treatment. |
| Surgery Delay Rate | From completion of Cycle 2 of neoadjuvant therapy (each cycle is 21 days) to the date of radical surgery. | Surgery delay rate is defined as the proportion of participants whose interval between the completion of the 2nd cycle of neoadjuvant therapy and radical surgery exceeds 4 weeks (interval \> 4 weeks) due to neoadjuvant therapy-related toxicities. |
| 1-Year Disease-Free Survival (DFS) Rate | From the date of radical surgery up to 1 year. | 1-Year disease-free survival (DFS) rate is defined as the proportion of participants who remain alive and free of any tumor recurrence (local or regional) or distant metastasis at 1 year following radical surgery |
| R0 Resection Rate | At the time of surgery, after completion of neoadjuvant treatment | The proportion of participants who achieve R0 resection among those undergoing definitive surgery. |
Countries
China
Contacts
CONTACTHuaju yang PhD
CONTACTXingchen Peng PhD
PRINCIPAL_INVESTIGATORXingchen Peng Peng, PhD
West China Hospital
Outcome results
None listed