JS001 Combined With TP as First-line Treatment for Unresectable or Advanced Small Cell Esophageal Carcinoma

Study Overview
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Brief Summary
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Small cell esophageal carcinoma (SCCE) is a kind of malignant tumor with poor prognosis. Our study found that the mutation spectrum and somatic CNV spectrum of SCCE were similar to those of esophageal squamous cell carcinoma (ESCC). Paclitaxel combined with cisplatin or carboplatin is the first-line treatment for ESCC. JS001 is a Chinese anti-PD-1 monoclonal antibody, which has been approved for the treatment of melanoma. This is a prospective, single arm, single center, phase II clinical trial of JS001 combined with nab-paclitaxel and cisplatin or carboplatin in the first-line treatment of unresectable or advanced SCCE. Aim to evaluate the safety and efficacy of this regimen in patients with unresectable or advanced SCCE.

Detailed Description
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Small cell esophageal carcinoma (SCCE) is a kind of malignant tumor with poor prognosis. Our previous studies found that the mutation spectrum and somatic CNV spectrum of SCCE were similar to those of esophageal squamous cell carcinoma (ESCC). Paclitaxel combined with cisplatin or carboplatin is a common first-line treatment for ESCC. In addition, some studies have shown that PD-1 mAb combined with paclitaxel chemotherapy in esophageal cancer has better efficacy and tolerability than chemotherapy alone. JS001 is a Chinese monoclonal antibody against PD-1 for injection, which has been approved for the treatment of melanoma. This is a prospective, single arm, single center, phase II clinical trial of JS001 combined with nab-paclitaxel and cisplatin or carboplatin in the first-line treatment of unresectable or advanced SCCE. Aim to evaluate the safety and efficacy of this regimen in patients with unresectable or advanced SCCE.

Official Title
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JS001 Combined With Nab-paclitaxel and Cisplatin or Carboplatin as First-line Treatment for Unresectable or Advanced Small Cell Esophageal Carcinoma : a Prospective, Single Arm, Single Center, Phase II Clinical Trial

Conditions
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Esophageal Small Cell Carcinoma

Intervention / Treatment
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* Drug: JS001
* Drug: nab-paclitaxel
* Drug: Cisplatin
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 18-75 years; Histologically or cytologically confirmed esophageal small cell carcinoma with unresectable locally advanced / recurrent or distant metastasis Patients who have not received systemic anti-tumor therapy Patients with recurrence or metastasis more than 6 months after the end of adjuvant or neoadjuvant chemotherapy accompanied by radical surgery or radical chemoradiotherapy; With at least 1 measurable lesion according to RECIST 1.1 criteria; ECOG score 0-1; Expected survival ≥3 months; Good organ function (without blood transfusion, use of hematopoietic stimulating factors, or transfusion of albumin or blood products within 7 days prior to examination): 1) Platelet (PLT) count ≥75,000 /mm3; 2) Neutrophil count (ANC) ≥1,500 /mm3; 3) Hemoglobin (Hb) level ≥9.0 g/dl; 4) Total bilirubin (TBIL) level ≤1.5×ULN; 5) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 6) Alkaline phosphatase level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 7) Serum creatinine (Cr) level ≤1.5×ULN and creatinine clearance >50 ml/min; Females of child bearing age must have anegative pregnancy test, and have to take contraception measures and for 3 months after the last dose Able to understand and willing to sign written informed consent form. Patients who agree to provide previously stored tumor tissue samples or perform biopsy to collect tumor tissue for gene testing. Exclusion Criteria: Known allergy to study drug or excipients, or allergy to similar drugs; Received anti-tumor cytotoxic drug therapy, biological drug therapy (such as monoclonal antibody), immunotherapy (such as interleukin-2 or interferon) or other research drug therapy within 4 weeks before enrollment. Received tyrosine kinase inhibitor treatment within 2 weeks before enrollment. Patients received radiotherapy within 4 weeks or radiopharmaceuticals within 8 weeks, except for local palliative radiotherapy for bone metastases. Major surgery was performed or not completely recovered from the previous surgery within 4 weeks before enrollment (the definition of major surgery refers to the level 3 and level 4 surgery specified in the administrative measures for clinical application of medical technology implemented on May 1, 2009). The toxicity of previous anti-tumor therapy has not recovered to CTCAE [version 4.03] 0-1, except for the following cases: a) lipsotrichia；b) Pigmentation;c) Peripheral neurotoxicity has recovered to < CTCAE 2;d) The long-term toxicity caused by radiotherapy could not be recovered according to the judgment of the researchers; Subjects with clinically symptomatic CNS metastases and/or cancerous meningitis. The subjects who have received brain or meningeal metastasis treatment in the past, if the clinical stability has been maintained for at least 2 months, and the systemic hormone treatment has been stopped for more than 4 weeks can be included. Have or are currently suffering from other malignancies (except for non melanoma basal cell carcinoma of the skin, breast / cervical carcinoma in situ, and other malignancies that have been effectively controlled without treatment in the past five years). Subjects have any active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or asthma in childhood who have completely remission and do not need any intervention in adulthood can be included; subjects with asthma requiring bronchodilator for medical intervention can not be included). Previous use of anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell costimulation or checkpoint pathway). Subjects with active pulmonary tuberculosis (TB) are receiving antituberculosis treatment or received antituberculosis treatment within one year before screening. Patients with complications requiring long-term use of immunosuppressive drugs or systemic or local use of corticosteroids with immunosuppressive effect (dose > 10mg / day of prednisone or other therapeutic hormones). Received any anti infection vaccine (such as influenza vaccine, varicella vaccine, etc.) within 4 weeks before enrollment. Pregnant or lactating women. HIV positive. HBsAg positive and HBV DNA copy number positive (quantitative detection ≥ 1000 CPS / ml). HCV antibody positive. Researchers believe that it can affect the compliance of the protocol, or affect the subject to sign the informed consent(ICF), or any other disease or condition of clinical significance that is not suitable to participate in this clinical trial. There are clinical symptoms or diseases that can not be well controlled, such as: (1) heart failure of NYHA grade 2 or above (2) unstable angina pectoris (3) myocardial infarction within one year (4) clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: JS001 Combined With TP as First-line Treatment for Unresectable or Advanced Esophageal Small Cell Carcinoma
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JS001 Combined With TP<br>recombinant humanized anti-PD-1 monoclonal antibody for injection (JS001) in combination with nab-paclitaxel and cisplatin or carboplatin for injection | Drug: JS001<br>* JS001 240mg, ivdrip, d1, Q3w<br>* Other names: recombinant humanized anti-PD-1 monoclonal antibody for injection;Drug: nab-paclitaxel<br>* nab-paclitaxel 220 mg/m2,ivdrip, d1,d8,Q3w<br>* Other names: Paclitaxel for injection (Albumin Bound);Drug: Cisplatin<br>* Cisplatin 75mg/m2, ivdrip,d1,Q3w<br>* Other names: Cisplatin for injection;Drug: Carboplatin<br>* Carboplatin AUC 5,d1,Q3w<br>* Other names: Carboplatin for injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Objective response rate (ORR)=CR+PR | from the initiation date of first cycle to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | PFS is the time measured from the date of initiation of treatment to the date of progression or death due to any cause, whichever occurs first. | from the initiation date of first cycle to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years | 
| Overall survival (OS) | Overall survival (OS) is the time calculated from the initiation of treatment to date of death or censored at last follow-up. | from the initiation date of first cycle to the date of date of death from any cause, assessed up to 2 years | 
| DCR | Disease control rate (DCR) =CR+PR+SD | from the initiation date of first cycle to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years | 
| Six-month progression-free survival rate | Six-month progression-free survival rate is the survival rate calculated at the end of the 6-month follow-up. | from the initiation date of first cycle to six months later | 
| One year survival rate | One year progression-free survival rate is the survival rate calculated at the end of the 1-year follow-up. | from the initiation date of first cycle to one year later | 
| Severe toxicity | Treatment-related adverse events. | from the initiation date of first cycle to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JS001, Nab-paclitaxel and, Cisplatin, Carboplatin, Small cell esophageal carcinoma