Esophageal Cancer by AJCC V8 Stage
Conditions
Brief summary
To evaluate the efficacy and safety of patients with advanced esophageal squamous cell carcinoma treated with camrelizumab combined with Apatinib mesylate plus short-course chemotherapy versus standard chemotherapy in first line
Interventions
DRUGCamrelizumab+Apatinib+Chemotherapy→Camrelizumab+Apatinib
camrelizumab 200 mg, i.v. d1,q3w; apatinib 250 mg, p.o. qd,q3w; cisplatin 25 mg/m2, i.v. d1-d3,q3w; According to investigator' choice： paclitaxel 135\ 150 mg/m2, i.v. d1,q3w; paclitaxel-albumin 150\ 180 mg/m2, i.v. d1,q3w. up to 4 cycles and sequential maintenance therapy： camrelizumab 200 mg, i.v. d1,q3w; apatinib 250 mg, p.o. qd,q3w
DRUGCamrelizumab+Chemotherapy→Camrelizumab
camrelizumab 200 mg, i.v. d1,q3w; cisplatin 25 mg/m2, i.v. d1-d3,q3w; According to investgator' choice： paclitaxel 175 mg/m2, i.v. d1,q3w; paclitaxel-albumin 200 mg/m2, i.v. d1,q3w up to 6 cycles and sequential maintenance therapy： camrelizumab 200 mg, i.v. d1,q3w;
Sponsors
The First Affiliated Hospital of Zhengzhou University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Age 18-75, male or female; * 2\. Esophageal squamous cell carcinoma that is histologically or cytologically confirmed as unresectable locally advanced/recurrent (unable to receive radical treatment such as radical chemoradiotherapy or radical radiotherapy) or distant metastasis; * 3\. No previous systematic antitumor therapy. For patients who received neoadjuvant/adjuvant and radical concurrent chemoradiotherapy, the time from the last chemotherapy to recurrence or progression more than 6 months can be screened; * 4\. According to the efficacy evaluation criteria for solid tumors (RECIST 1.1), there should be at least one measurable lesion (esophageal and other cavity structures cannot be used as measurable lesions), and the measurable lesions should not have received local treatment such as radiotherapy (lesions located within the previous radiotherapy area can also be selected as target lesions if it is confirmed to progress); * 5\. Agree to provide tissue samples for biomarker (such as PD-L1) analysis. Recently obtained tissues are preferred. Patients who cannot provide recently obtained tissues can provide 5-8 paraffin sections of 3-5 μm thickness for archival storage; * 6\. ECOG PS: 0 \ 1; * 7\. Swallowing pills normally; * 8\. Expected survival ≥12 weeks; * 9\. The functions of vital organs meet the following requirements (no drugs with blood components and cell growth factors are allowed to be used within 14 days before the first use of the study drug); 1. Absolute count of neutrophils (ANC) ≥1.5×109/L 2. Platelet ≥90×109/L; 3. Hemoglobin ≥90g/L; 4. Serum albumin ≥28g/L; 5. Total bilirubin ≤1.5 × ULN, ALT, AST, and/or AKP≤2.5 × ULN; If liver metastasis is present, ALT and/or AST≤5 × ULN; If there is liver metastasis or bone metastasis AKP≤5 × ULN; 6. Serum creatinine ≤1.5 × ULN or creatinine clearance \> 60 mL/min (Cockcroft-Gault); 7. Activated partial thromboplastin time (APTT) and International Normalized ratio (INR) ≤1.5 × ULN (for stable dose anticoagulant therapy such as low molecular weight heparin or warfarin and INR within the expected treatment range of anticoagulants can be screened) * 10\. Fertile female subjects and male subjects whose partners are women of childbearing age, A medically approved contraceptive (such as an intrauterine device, contraceptive or condom) is required during the study treatment period and at least 2 months after the last use of carrilizumab/Apatinib mesylate and at least 6 months after the last use of chemotherapy; * 11\. The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up.
Exclusion criteria
* 1\. BMI \< 18.5 kg/m2 or weight loss ≥10% within 2 months prior to screening (while the effect of large amounts of abdominal and thoracic fluids on body weight should be considered); * 2\. Active hemoptysis occurred within 3 weeks before the first administration of the study drug, or tumor hemorrhage occurred within 2 weeks before the first administration of the study intervention; * 3\. Patients with tumors assessed by the investigator to have invaded adjacent organs of the esophageal lesion (such as the aorta or respiratory tract) and had a high risk of bleeding or fistula during the study; * 4\. Previous history of gastrointestinal perforation and/or fistula or recent (within 3 months before randomization) history of intestinal obstruction or imaging and clinical symptoms suggestive of intestinal obstruction; * 5\. Subjects who have had esophageal stents implanted or are evaluated for needing esophageal stents implanted; * 6\. Patients with clinical symptoms of pleural effusion, pericardial effusion or ascites who need puncture or drainage or who have received drainage for treatment within 1 month before randomization; * 7\. Have high blood pressure that is not well controlled by antihypertensive medications (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) * 8\. A history of allergies to monoclonal antibodies, any component of Camrelizumab, Apatinib mesylate and its excipients, paclitaxel, albumin paclitaxel and cisplatin; * 9\. Received any of the following medical treatment: 1. Received any investigational drug within 4 weeks prior to initial use of the investigational drug; 2. Enrolling in another clinical study at the same time, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up; 3. Receiving the last dose of anticancer therapy (including radiotherapy, etc.) within 4 weeks or less before the first use of the study drug; 4. Subjects who required systemic treatment with corticosteroids (\> 10 mg daily equivalent of prednisone) or other immunosuppressant within 2 weeks prior to initial use of the study drug, except for corticosteroids for local esophageal inflammation and prevention of allergy, nausea, and vomiting. In the absence of active autoimmune disease, inhaled or topical steroid and adrenocortical hormone replacement at doses \> 10mg/ day of prednisone efficacy dose are permitted; 5. Those who have received anti-tumor vaccine or have received live vaccine within 4 weeks prior to the first administration of the study drug; 6. Major surgery or severe trauma within 4 weeks prior to initial use of the study drug; * 10\. The toxicity of previous antitumor therapy has not recovered to ≤CTCAE Grade 1 (except hair loss) or the level specified by inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS[Progression-Free Survival] | up to 2 year | Time from randomization to first radiographic disease progression (RECIST 1.1 criteria) or death, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR[Objective Response Rate] | up to 1 year | Proportion of subjects in the analysis population who achieved complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. |
| DCR[Disease Control Rate] | up to 1 year | Proportion of subjects in the analysis population who achieved complete response (CR) , partial response (PR) or stable disease(SD) based on RECIST 1.1 criteria. |
| OS[Overall Survival] | up to 2 year | Time from randomization to the subject's death. At the end of the study, if the subject is still alive, the last known date of survival of the subject will be the date of deletion. |
| DoR[Duration of response] | up to 2 year | For subjects who achieved remission, the time from first achieving CR or PR to disease progression or death, whichever occurred earlier. |
| AEs[Adverse events] | up to 2 year | The incidence and severity of adverse events (AE) and serious adverse events (SAE) were determined according to NCI-CTCAE v5.0 criteria. |
| TTR[Time to response] | up to 1 year | Time from randomization to firstly achieve CR or PR based on RECIST 1.1 criteria. |
Countries
China
Contacts
Primary ContactFeng Wang, phD
Outcome results
None listed