A Randomized, Open-label, Controlled, Multicenter Phase II Trial of Anrotenib Plus Toripalimab Versus Toripalimab for Following Treatment of Advanced Esophageal Squamous Cell Carcinoma After Chemotherapy Failure
Overview
- Phase
- Phase 2
- Intervention
- Anrotenib plus Toripalimab
- Conditions
- Esophageal Squamous Cell Carcinoma
- Sponsor
- Henan Cancer Hospital
- Enrollment
- 164
- Primary Endpoint
- Overall Survival (OS)
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Confirmed esophageal squamous cell carcinoma patients by histopathological or cytopathological examinations.
- •Advanced esophageal squamous cell carcinoma patients with progression after chemotherapy of taxol and/or platinum or fluorouracil.
- •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).
- •A histological specimen can be provided for secondary testing.
- •≥18 years old, male or female.
- •ECOG performance status 0-
- •Life expectancy ≥ 12 weeks.
- •The main organ function meets the following criteria within 7 days before treatment:
- •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.
- •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.
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.
- •History of gastrointestinal perforation and/or fistula within 6 months prior to the first administration.
- •Esophageal lesion obviously invading the adjacent organs (major arteries or trachea), resulting in a higher risk of bleeding or fistula.
- •Received any of the following treatment:
- •Previous treatment with anti-PD-1 antibodies or anti-PD-L1 antibodies;
- •Received any experimental drug within 4 weeks prior to the first administration of the study drug;
- •Enroll in another clinical study, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up;
- •Receive the last dose of anticancer therapy (including radiotherapy, etc.) within 4 weeks before the first administration of the study drug;
- •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;
- •Received an anti-tumor vaccine or received a live vaccine within 4 weeks prior to the first administration of the study drug
Arms & Interventions
Anrotenib 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; Until disease progression according to the RECIST 1.1 and irRECIST standard, intolerance of toxicity, withdrawal of informed consent from the subject, or tripleuriumab administration up to 2 years.
Intervention: Anrotenib plus Toripalimab
Toripalimab
Toripalimab: 240 mg on day 1 intravenously repeated every 21 days; Until disease progression according to the RECIST 1.1 and irRECIST standard, intolerance of toxicity, withdrawal of informed consent from the subject, or tripleuriumab administration up to 2 years.
Intervention: Toripalimab
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: up to 2 years
From the first day of treatment to death or last survival confirm date
Secondary Outcomes
- Progression-free Survival (PFS)(up to 2 years)
- Objective Response Rate (ORR)(up to 2 years)
- Disease Control Rate (DCR)(up to 2 years)
- Number of Participants with Treatment-related Adverse Events Treatment-related adverse events(up to 2 years)
- Assessment of Health-related quality of life(up to 2 years)