Esophageal Squamous Cell Carcinoma
Conditions
Brief summary
The aim of this study is to investigate the efficacy and safety of anrotenib plus toripalimab in the treatment of advanced esophageal squamous cell carcinoma. In addition, the investigators will explore the possible mechanisms of anrotinib combined with toripalimab in advanced esophageal squamous cell carcinoma, and screen out biomarkers that can predict the efficacy of combination therapy.
Detailed description
There is no standard recommendation for the treatment of advanced esophageal squamous cell cancer after chemotherapy failure. Anrotinib combined with triplizumab have showed synergistic effect in the tumor treatment, and they have demonstrated robust antitumor activity in the first-line treatment of advanced NSCLC with negative driving gene. However, there is no related report on the efficacy in the treatment of advanced esophageal squamous cell carcinoma. The aim of this study is to investigate the efficacy and safety of anrotenib plus toripalimab in the treatment of advanced esophageal squamous cell carcinoma. In addition, the investigators will explore the possible mechanisms of anrotinib combined with toripalimab in advanced esophageal squamous cell carcinoma, and screen out biomarkers that can predict the efficacy of combination therapy.
Interventions
DRUGAnrotenib plus Toripalimab
Anrotenib: 10 mg on day 1-14 orally repeated every 21 days; Toripalimab: 240 mg on day 1 intravenously repeated every 21 days.
DRUGToripalimab
Toripalimab: 240 mg on day 1 intravenously repeated every 21 days.
Sponsors
Henan Cancer Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Confirmed esophageal squamous cell carcinoma patients by histopathological or cytopathological examinations. * 2\. Advanced esophageal squamous cell carcinoma patients with progression after chemotherapy of taxol and/or platinum or fluorouracil. * 3\. According to the evaluation criteria of solid tumor efficacy (RESIST 1.1), there should be at least one measurable lesion (empty organs such as esophagus and stomach cannot be taken as the measurable lesion), and the measurable lesion should not have received local treatment such as radiotherapy (the lesion located in the previous radiotherapy area is also selected as the target lesion if the lesion progression is confirmed). * 4\. A histological specimen can be provided for secondary testing. * 5\. ≥18 years old, male or female. * 6\. ECOG performance status 0-1. * 7\. Life expectancy ≥ 12 weeks. * 8\. The main organ function meets the following criteria within 7 days before treatment: 1. Blood routine examination criteria (without blood transfusion within 14 days): hemoglobin (HB) ≥ 90g/L, the absolute value of neutrophils (ANC) ≥ 1.5 x 10\^9/L, platelet (PLT) ≥ 80 x 10\^9/L. 2. Biochemical examinations must meet the following criteria: total bilirubin (TBIL) ≤ 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x ULN, serum creatinine (Cr) ≤ 1.5 x ULN or creatinine clearance (CCR) ≥ 60 mL/min. 3. Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%). * 9\. Fertile men and women must use effective contraception during the study period and within 6 months after the end of the study. * 10\. The patient volunteered to participate in the study and signed an informed consent form.
Exclusion criteria
* 1.Patients exceeding or currently suffering from other malignant tumors within 5 years, except for cervical cancer in site, non-melanoma skin cancer and superficial bladder tumors (Ta (non-invasive tumor), Tis (in situ carcinoma), and T1 (tumor infiltrating basement membrane)); Patients with rapid progress within 3 months. * 2\. History of gastrointestinal perforation and/or fistula within 6 months prior to the first administration. * 3\. Esophageal lesion obviously invading the adjacent organs (major arteries or trachea), resulting in a higher risk of bleeding or fistula. * 4\. Received any of the following treatment: 1. Previous treatment with anti-PD-1 antibodies or anti-PD-L1 antibodies; 2. Received any experimental drug within 4 weeks prior to the first administration of the study drug; 3. Enroll in another clinical study, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up; 4. Receive the last dose of anticancer therapy (including radiotherapy, etc.) within 4 weeks before the first administration of the study drug; 5. Patients who need to be given corticosteroids (the equivalent dose of \> 10 mg prednisone per day) or other immunosuppressants for systemic treatment within 2 weeks prior to the first use of the study drug, except the use of corticosteroids for esophageal local inflammation and the prevention of allergies, nausea and vomiting. In the absence of active autoimmune disease, inhaled or topical corticosteroid of an equivalent dose of \> 10mg prednisone per day is permitted; 6. Received an anti-tumor vaccine or received a live vaccine within 4 weeks prior to the first administration of the study drug 7. Received major surgery or severe trauma within 4 weeks prior to first administration of the study drug. * 5\. History of immunodeficiency disease, including HIV positive and other acquired or congenital immunodeficiency diseases, or history of organ transplantation allogeneic bone marrow transplantation. * 6\. Toxicity of previous antitumor treatment did not return to the level ≤NCI CTC AE V5.0 grade 1 (except alopecia) or to the level specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | up to 2 years | From the first day of treatment to death or last survival confirm date |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | up to 2 years | From the first day of treatment until the date of first documented progression or date of death from any cause |
| Objective Response Rate (ORR) | up to 2 years | To compare objective response rate of the two arms from date of anti-cancer therapy until progression |
| Disease Control Rate (DCR) | up to 2 years | To compare disease control rate of the two arms from date of anti-cancer therapy until progression |
| Number of Participants with Treatment-related Adverse Events Treatment-related adverse events | up to 2 years | Number of Participants with Treatment-related Adverse Events Treatment-related adverse events will be assessed by NCI CT CAE v5.0 |
| Assessment of Health-related quality of life | up to 2 years | Quality of Life Questionnaire (QLQ-C30) will be evaluated since treatment begins. At the end of the trail, the differences between the two indicators will be compared with Mixed-effects model repeated measures (MMRM), where the baseline is scored as a covariant and the treatment group as a fixed variable. In addition, the baseline values of the two scores, the value of each visit, and the change value of the baseline will be statistically described. |
Contacts
Primary ContactYing Liu
Outcome results
None listed