Esophageal Squamous Cell Carcinoma
Conditions
Brief summary
The purpose of this study is to observe and evaluate the efficacy and safety of anlotinib combined with sindilimab as second-line treatment for advanced esophageal squamous cell carcinoma (ESCC). In addition, we also explored the possible mechanism of anlotinib combined with sindilimab in order to screen out biomarkers that can predict the efficacy of the combination therapy.
Detailed description
China is one of the regions with the highest risk of esophageal cancer in the world, and more than 90% of esophageal cancer is squamous cell carcinoma (SCC). The incidence of esophageal cancer is ranked sixth and the mortality rate ranks fourth in China. At present, the first-line treatment of advanced esophageal cancer is mainly based on the combination of paclitaxel, cisplatin and fluorouracil. After the failure of first-line treatment, there is no standard second-line treatment. The investigators designed a multicenter, single-arm, open-label phase Ⅱ clinical trial of anlotinib combined with sindilimab as second-line treatment for advanced esophageal squamous cell carcinoma (ESCC).
Interventions
DRUGAnlotinib + Sintilimab
Anlotinib: 1 capsule (10mg) once a day, d1-d14 per cycle, 3 weeks for a treatment cycle. Sintilimab: 200 mg/time, intravenous injection, every 3 weeks is one cycle.
Sponsors
Henan Provincial People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Pathologically (histologically or cytologically) confirmed diagnosis of esophageal squamous cell carcinoma (excluding mixed type adenosquamous carcinoma ) * Patients undergoing first-line systemic chemotherapy (which may include taxanes, platinum and fluorouracil) progression. For radical concurrent chemoradiotherapy, neoadjuvant/adjuvant therapy (chemotherapy or chemoradiotherapy), if disease progression occurs during treatment or within 6 months after stopping treatment, Count it as a first-line treatment failure.（Note: Patients with advanced or relapsed non target lesions who progress again after radiotherapy alone are included. Palliative treatment for local lesions (non target lesions) lasted for more than 2 weeks.） * At least one measurable/evaluable lesion by RECIST v1.1（Cavity organ such as esophagus can not be used as measurable lesions）. And the measurable lesions should not have received local treatment such as radiotherapy (The lesion located in the previous radiotherapy area, if confirmed to progress, and meets the RECIST 1.1 standard, can also be used as a target lesion). * 18\ 80 years, both men and women. * Patients who can provide histological specimens for pathological review. * Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1. * Life expectancy of ≥ 12 weeks. * The main organs function normally, that is, the following criteria are met: (1) Blood routine examination: 1. HB≥90g/L; 2. ANC ≥ 1.5 × 109 / L; 3. PLT ≥ 80 × 109 / L. (2) Biochemical examination: 1. TBIL ≤ 1.5ULN 2. ALT and AST ≤ 2.5ULN 3. plasma Cr ≤ 1.5ULN or creatinine clearance (CCr) ≥ 60ml / min 4. left ventricular ejection fraction (LVEF)≥ normal low limit (50%) * Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative before enrollment；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped. * Patients should participate in the study voluntarily and sign informed consent.
Exclusion criteria
* The patients who had or were suffering from other malignant tumors within 5 years, except for the cured cervical carcinoma in situ, non melanoma skin cancer and superficial bladder tumor \[ta (non-invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)\] and those who developed rapidly within 3 months. * Patients with a history of perforation and / or fistula within 6 months before the first medication. * Patients with a high risk of bleeding or perforation due to the apparent invasion of adjacent organs (aorta or trachea) of the esophageal lesion, or patients who have formed fistulas. * Have received any of the following treatments: 1. Patients who received Sindilimab therapy or other immunotherapy against PD-1/PD-L1. 2. Patients who have participated in other drug clinical trials within four weeks. 3. Enter another clinical study, unless it is an observational (non intervention) clinical study or an intervention clinical study. 4. Receive the last dose of anticancer treatment (including radiotherapy, etc.) within ≤ 4 weeks before the first use of the study drug. 5. The patient is using immunosuppressive agents or systemic hormonal therapy for immunosuppression purposes (dose \>10 mg/day of prednisone ) and continues to be used within 2 weeks prior to enrollment, except for the use of corticosteroids for local esophageal inflammation and prevention of allergy, nausea and vomiting. In the absence of active autoimmune diseases, inhaled or topical corticosteroids and corticosteroid replacement with a therapeutic dose of prednisone greater than 10 mg / day are permitted. 6. Patients who had been vaccinated with anti-tumor vaccine or had been vaccinated with live vaccine within 4 weeks before the first administration of the study drug. 7. The patient had major surgery or severe trauma within 4 weeks before the first use of the study drug. * A history of immunodeficiency, including a positive HIV test or other acquired, congenital immunodeficiency disease, or a history of organ transplantation. * The toxicity of previous anti-tumor therapy did not return to ≤ NCI CTC AE v5.01 (except alopecia) or the level specified in the inclusion /
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival(OS) | up to 2 year | From date of randomization until the date of death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progress free survival (PFS) | up to 2 year | From date of randomization until the date of first documented progression or date of death from any cause |
| Objective Response Rate (ORR) | up to 1 year | From date of randomization until the date of death from any cause |
| Disease Control Rate (DCR) | up to 1 year | Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) |
Contacts
Primary ContactJianwei Zhou, Doctor
Outcome results
None listed