Phase II Clinical Study of Camrelizumab Combined With Chemotherapy or Anlotinib in Advanced Esophageal Squamous Cell Cancer

University of Chinese Academy Sciences

Status and phase: Not yet enrolling; Phase 2

Conditions: Stage IV Esophagus Squamous Cell Carcinoma

Treatments: Drug: Paclitaxel-albumin; Drug: Paclitaxel; Drug: Irinotecan; Drug: Docetaxel; Drug: Camrelizumab; Drug: Anlotinib

Study type: Interventional

Funder types: Other

Identifiers

NCT05322499

IRB-2021-444

Details and patient eligibility

About

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

Full 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.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 18-75 years old, male or female;
2. 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.);
3. Patients with advanced esophageal squamous cell carcinoma diagnosed as stage IV by histopathology or cytology;
4. ECOG PS score of physical condition: 0-1 points;
5. Expected survival period ≥ 3 months;
6. 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;
7. 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; 8. 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; 9. Those who have not participated in clinical trials of other drugs within 4 weeks before enrollment; 10. Patients with good compliance are expected to be able to follow up the efficacy and adverse reactions according to the requirements of the program; 11. In view of the unclear definition of primary drug resistance and the lack of standard treatment options for such patients, there is a potential possibility of benefiting such patients with immunization combined with anti-angiogenesis or chemotherapy, but there is also a certain risk of hyperprogression; Therefore, for patients with possible primary drug resistance, they must be included in the group after evaluation by the investigator.

Exclusion criteria

1. Other malignant tumors have been diagnosed in the past 5 years;
2. Patients with active bleeding within two months of the primary tumor;
3. Patients with severe adverse reactions related to immunotherapy after previous use of immunotherapy;
4. 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. );
5. Suffering from uncontrolled clinical symptoms or diseases of the heart;
6. Active infection or fever (except for definite tumor fever);
7. History or evidence of interstitial lung disease or active non-infectious pneumonia;
8. 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;
9. Those who have not participated in clinical trials of other drugs within 4 weeks before enrollment;
10. Patients with good compliance are expected to be able to follow up the efficacy and adverse reactions according to the requirements of the program;
11. In view of the unclear definition of primary drug resistance and the lack of standard treatment options for such patients, there is a potential possibility of benefiting such patients with immunization combined with anti-angiogenesis or chemotherapy, but there is also a certain risk of hyperprogression; Therefore, for patients with possible primary drug resistance, they must be included in the group after evaluation by the investigator.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Combined chemotherapy group

Experimental group

Description:

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

Treatment:

Drug: Docetaxel

Drug: Camrelizumab

Drug: Irinotecan

Drug: Paclitaxel

Drug: Paclitaxel-albumin

Combined anlotinib group

Experimental group

Description:

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.

Treatment:

Drug: Anlotinib

Drug: Camrelizumab