Esophageal squamous cell carcinoma
Conditions
Interventions
Experimental group:Anlotinib: starting dose 12 mg orally once daily (taken before breakfast on an empty stomach
dosing should occur at approximately the same time each day). Administer for 2 consecutive weeks followed by 1 week off
every 21 days constitutes one treatment cycle.
For intolerant patients, the dose may be reduced stepwise to 10 mg or 8 mg.
Bemelstobart injection: 1200 mg diluted in 250 mL of 0.9 % sodium chloride
patients who reach 2 years will be automatically discontinued from the study.
Control Group:Second-line single-agent chemotherapy, selected at the physician’s discretion:
- Paclitaxel 175 mg/m2 IV, Day 1, every 3 weeks
- Docetaxel 75–100 mg/m2 IV, Day 1, every 3 weeks
- N
Sponsors
The First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18–75 years, both sexes eligible; 2. Histologically confirmed unresectable locally advanced, recurrent, or metastatic esophageal squamous-cell carcinoma (adenosquamous or mixed histologies excluded); 3. Progression or intolerance after first-line chemotherapy combined with a PD-1 immune-checkpoint inhibitor; 4. Eastern Cooperative Oncology Group (ECOG) performance status 0–1; 5. Life expectancy > 3 months; 6. At least one measurable lesion per RECIST 1.1 that can be accurately assessed in at least one dimension (longest diameter recorded) by MRI or CT; baseline longest diameter = 10 mm (= 15 mm short axis for lymph nodes). Lesions must not have received prior local therapy such as radiotherapy (lesions within a previously irradiated field may be selected as target lesions if progression has been documented and RECIST 1.1 criteria are met); 7. Adequate organ function as defined by the following laboratory values at screening: (1). Hematological parameters must meet the following criteria: 1). Haemoglobin (Hb) >= 80 g/L without transfusion within 14 days; 2). Absolute neutrophil count (ANC) >= 1.5 × 10^9/L; 3). Platelet count (PLT) >= 75 × 10^9/L without IL-11 or TPO within 14 days; 4). White-blood-cell count (WBC) >= 3.0 × 10^9/L without G-CSF within 14 days; (2). Biochemical tests must meet the following criteria: 1). Total bilirubin (TBIL) = 60 mL/min; 4). Coagulation: INR or PT = institutional lower limit of normal (50 %); 6) Cardiac enzymes: within normal limits; 8. Women of child-bearing potential (WOCBP) must use highly effective contraception from screening through 3 months after the last study dose and must not be breast-feeding. A negative serum or urine pregnancy test within 7 days before enrolment is required, OR evidence of non-child-bearing potential as follows: (1). Post-menopausal: age > 50 years and amenorrhoea for >= 12 months after cessation of all exogenous hormonal therapy; (2). Women = 12 months after stopping exogenous hormones and FSH plus LH in the post-menopausal laboratory range; (3). Documented irreversible sterilisation: hysterectomy, bilateral oophorectomy, or bilateral salpingectomy; tubal ligation alone is insufficient; 9. Men must agree to use effective contraception from first dose through 8 weeks after the last dose or be surgically sterile
Exclusion criteria
Exclusion criteria: 1. Prior treatment with anlotinib hydrochloride or benmelstobart; 2. Prior therapy with any anti-angiogenic agent or immune-checkpoint inhibitor (PD-L1 or CTLA-4), alone or in combination/sequence; 3. Concurrent or previous malignancy(ies) diagnosed during the ESCC period, except: a) Malignancy in complete remission >= 2 years before enrollment and not requiring further therapy during the study; b) Adequately treated non-melanoma skin cancer or lentigo maligna without recurrence; c) Adequately treated carcinoma in situ without recurrence; 4. Traditional Chinese medicine with anti-tumor intent within 2 weeks before screening, if the formulation contains any of: brucea fruit, coix seed, lentinan, cantharides, toad skin, astragalus, sophora flavescens, marsdenia tenacissima, chebula, icariin, etc. Patients are eligible if the last dose of such traditional Chinese medicine ended > 2 weeks before enrollment; 5. History of immunodeficiency, including HIV-positive status or any acquired/congenital immunodeficiency disorder; 6. Contra-indications to re-initiation of immunotherapy; 7. Tumor clearly invading adjacent esophageal structures (major artery or trachea) conferring high risk of hemorrhage or perforation, or established fistula; 8. Prior allogeneic bone-marrow or organ transplantation; 9. Idiopathic pulmonary fibrosis, drug-related pneumonitis, organizing pneumonia, or CT-proven active pneumonia; 10. Known symptomatic central-nervous-system (CNS) metastases and/or carcinomatous meningitis. Patients with treated CNS metastases or spinal cord compression may enroll if clinically stable for = 4 weeks after stopping anticonvulsants and steroids; 11. Peripheral neuropathy >= Grade 2 (NCI CTCAE); 12. Infection requiring systemic antibiotics within 14 days before first dose; 13. Bone metastases with imminent risk of paraplegia; 14. Any severe or uncontrolled medical condition, including: (1). Uncontrolled hypertension (systolic >= 150 mmHg or diastolic >= 100 mmHg) despite medication; Grade >= 2 myocardial ischemia/infarction or arrhythmia (including QTc >+ 480 ms); NYHA Class III–IV heart failure or LVEF 10 mmol/L); (3). Urinalysis >= ++ proteinuria confirmed by 24-h urine protein > 1.0 g; 15. Major surgery (craniotomy, thoracotomy, laparotomy) within 4 weeks before screening, or anticipated need for major surgery during the study; non-diagnostic surgery within 4 weeks is also excluded. 16. Clinically significant pleural/peritoneal effusion (detectable on physical exam or requiring/recently required intervention). Asymptomatic minimal effusion seen only on imaging is permitted if investigator judges no treatment necessary; 17. BMI = 10 % weight loss within 2 months before screening; 18. History of substance abuse with psychotropic agents that cannot be discontinued, or psychiatric disorder compromising compliance; 19. CT evidence of definite ulcerative lesion or fecal occult blood >= ++; 20. History of abnormal bleeding (except epistaxis) within 1 month before enrollment; 21. Pregnant or lactating women; 22. Any severe concomitant condition that, in the investigator’s opinion, jeopardizes patient safety or precludes protocol compliance; 23. Participation in another clinical trial within 30 days before screening or intention to join another trial during the present study;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival;Objective Response Rate;Disease Control Rate;Duration of Response;Safety; | — |
Countries
China
Contacts
Public ContactZhi-Wei Chang
The First Affiliated Hospital of Zhengzhou University
Outcome results
None listed