Phase II Clinical Study of Camrelizumab Combined With Chemotherapy or Anlotinib in Second-line or Above Therapy for Advanced Esophageal Squamous Cell Cancer Previously Treated With First-line Immunotherapy
Overview
- Phase
- Phase 2
- Intervention
- Paclitaxel-albumin
- Conditions
- Stage IV Esophagus Squamous Cell Carcinoma
- Sponsor
- Zhejiang Cancer Hospital
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Not yet recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
To observe and evaluate the efficacy and safety of camrelizumab combined with chemotherapy or anlotinib in patients with advanced esophageal squamous cell carcinoma previously Treated With First-line Immunotherapy
Detailed Description
How to improve the efficacy of immunotherapy, evaluate the results of immunotherapy more objectively, and overcome immune resistance through reasonable combined treatment methods, so as to maximize the benefit of patients from immunotherapy, is an urgent research direction to be explored. Therefore, this study intends to observe and evaluate the efficacy and safety of camrelizumab combined with chemotherapy or anlotinib in patients with advanced esophageal squamous cell cancer previously Treated With First-line Immunotherapy . It can provide a basis for the treatment of esophageal cancer after immune resistance.
Investigators
Yu Xinmin
Physician
Zhejiang Cancer Hospital
Eligibility Criteria
Inclusion Criteria
- •Age 18-75 years old, male or female;
- •Participants signed and dated written informed consent. (Informed consent forms must be signed prior to any protocol-related procedures that are not part of the participant's routine medical care.);
- •Patients with advanced esophageal squamous cell carcinoma diagnosed as stage IV by histopathology or cytology;
- •ECOG PS score of physical condition: 0-1 points;
- •Expected survival period ≥ 3 months;
- •Patients with esophageal squamous cell carcinoma who have received first-line or above systemic therapy in the past, and who have received at least 2 times of PD-1 immunotherapy;
- •Laboratory inspection indicators meet the following requirements:
- •(1) Bone marrow function: hemoglobin (Hb) ≥ 90g/L; white blood cell count (WBC) ≥ lower limit of normal; absolute neutrophil value (ANC) ≥ 1.5×10\^9 /L; platelet count ≥ 100×10\^9 / L; (2) Renal function: Cr≤UNL (upper limit of normal)×1.5, endogenous creatinine clearance rate (Ccr)≥55 ml/min; (3) Liver function: total bilirubin≤ULN×1.5; ALT and AST≤ULN×2.5; (4) Coagulation function: the international normalized ratio of prothrombin time is less than or equal to ULN×1.5, and the partial thromboplastin time is within the normal range;
- •Females of childbearing age agree to contraception during the study period and within 6 months after the end of the study; serum or urine pregnancy test is negative within 7 days before the study is enrolled, and non-lactating patients; males agree to use contraception during the study period and within 6 months after the end of the study contraceptive patients;
- •Those who have not participated in clinical trials of other drugs within 4 weeks before enrollment;
Exclusion Criteria
- •Other malignant tumors have been diagnosed in the past 5 years;
- •Patients with active bleeding within two months of the primary tumor;
- •Patients with severe adverse reactions related to immunotherapy after previous use of immunotherapy;
- •Patients with any active autoimmune disease or autoimmune disease (including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis, vascular inflammation, glomerulonephritis, uveitis, hypophysitis, hyperthyroidism, etc.). Type 1 diabetes mellitus receiving stable doses of insulin, hypothyroidism receiving only hormone replacement therapy, no systemic therapy required, and no acute exacerbation of skin disease (eg, eczema, vitiligo, or psoriasis) within 1 year prior to the screening period. );
- •Suffering from uncontrolled clinical symptoms or diseases of the heart;
- •Active infection or fever (except for definite tumor fever);
- •History or evidence of interstitial lung disease or active non-infectious pneumonia;
- •Females of childbearing age agree to contraception during the study period and within 6 months after the end of the study; serum or urine pregnancy test is negative within 7 days before the study is enrolled, and non-lactating patients; males agree to use contraception during the study period and within 6 months after the end of the study contraceptive patients;
- •Those who have not participated in clinical trials of other drugs within 4 weeks before enrollment;
- •Patients with good compliance are expected to be able to follow up the efficacy and adverse reactions according to the requirements of the program;
Arms & Interventions
Combined chemotherapy group
Camrelizumab: Subjects were infused at a dose of 200 mg/time, D1, once every 3 weeks (q3w); Chemotherapy (considered by investigator on a patient-by-patient basis): Irinotecan: 100-125mg/m2, d1, d8; q21d; Paclitaxel: 135-175mg/m2, d1, Q3W; Docetaxel: 60-75mg/m2, d1, Q3W Albumin paclitaxel: 100-135mg/m2, d1, d8, Q3W. Treat until disease progression or intolerable toxicity
Intervention: Paclitaxel-albumin
Combined chemotherapy group
Camrelizumab: Subjects were infused at a dose of 200 mg/time, D1, once every 3 weeks (q3w); Chemotherapy (considered by investigator on a patient-by-patient basis): Irinotecan: 100-125mg/m2, d1, d8; q21d; Paclitaxel: 135-175mg/m2, d1, Q3W; Docetaxel: 60-75mg/m2, d1, Q3W Albumin paclitaxel: 100-135mg/m2, d1, d8, Q3W. Treat until disease progression or intolerable toxicity
Intervention: Camrelizumab
Combined chemotherapy group
Camrelizumab: Subjects were infused at a dose of 200 mg/time, D1, once every 3 weeks (q3w); Chemotherapy (considered by investigator on a patient-by-patient basis): Irinotecan: 100-125mg/m2, d1, d8; q21d; Paclitaxel: 135-175mg/m2, d1, Q3W; Docetaxel: 60-75mg/m2, d1, Q3W Albumin paclitaxel: 100-135mg/m2, d1, d8, Q3W. Treat until disease progression or intolerable toxicity
Intervention: Irinotecan
Combined chemotherapy group
Camrelizumab: Subjects were infused at a dose of 200 mg/time, D1, once every 3 weeks (q3w); Chemotherapy (considered by investigator on a patient-by-patient basis): Irinotecan: 100-125mg/m2, d1, d8; q21d; Paclitaxel: 135-175mg/m2, d1, Q3W; Docetaxel: 60-75mg/m2, d1, Q3W Albumin paclitaxel: 100-135mg/m2, d1, d8, Q3W. Treat until disease progression or intolerable toxicity
Intervention: Paclitaxel
Combined chemotherapy group
Camrelizumab: Subjects were infused at a dose of 200 mg/time, D1, once every 3 weeks (q3w); Chemotherapy (considered by investigator on a patient-by-patient basis): Irinotecan: 100-125mg/m2, d1, d8; q21d; Paclitaxel: 135-175mg/m2, d1, Q3W; Docetaxel: 60-75mg/m2, d1, Q3W Albumin paclitaxel: 100-135mg/m2, d1, d8, Q3W. Treat until disease progression or intolerable toxicity
Intervention: Docetaxel
Combined anlotinib group
Camrelizumab: Subjects were infused at a dose of 200 mg/time, D1, once every 3 weeks (q3w); Anlotinib: 12mg, qd, d1-d14, q3w; Treat until disease progression or intolerable toxicity.
Intervention: Camrelizumab
Combined anlotinib group
Camrelizumab: Subjects were infused at a dose of 200 mg/time, D1, once every 3 weeks (q3w); Anlotinib: 12mg, qd, d1-d14, q3w; Treat until disease progression or intolerable toxicity.
Intervention: Anlotinib
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: Up to 24 month
ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Secondary Outcomes
- Duration of response (DoR)(Up to 24 month)
- Disease control rate (DCR)(Up to 24 month)
- Progression-free survival (PFS)(Up to 24 month)
- Overall survival (OS)(Up to 24 month)