Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Cisplatin and Capecitabine for Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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Surgical resection is currently the major treatment for esophageal carcinoma while disease progression still occurred in most cases within 3 years. The rate of local recurrence and distant metastases could reach nearly 40% to 60%. The neoadjuvant chemotherapy could significantly improve resection rate and overall survival after surgery. Squamous cell carcinoma is the most common histology in Asia. JCOG9907 trial performed in Japan confirmed that compared to surgery plus adjuvant chemotherapy, the combination of neoadjuvant chemotherapy and surgery could further prolong overall survival. The regimen of cisplatin and fluorouracil is a classic effective option in combination therapy for esophageal carcinoma. Nanoparticle albumin-bound (nab)-paclitaxel is a novel taxane and has better efficacy in esophageal carcinoma treatment. We try to evaluate the efficacy and safety of neoadjuvant chemotherapy with nab-paclitaxel plus cisplatin and capecitabine for locally advanced thoracic esophageal squamous cell carcinoma patients.

Official Title
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Phase II Study of Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Cisplatin and Capecitabine for Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: nab-paclitaxel
* Drug: Cisplatin
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic pathological or cytological diagnosis of squamous cell carcinoma of esophagus Age ranges from 18 to 70 years Patients must not have received any prior anticancer therapy Preoperative stage cT2N+M0, cT3-4aN0/N+M0 thoracic esophageal squamous cell carcinoma evaluated by MDT consultation based on imaging examinations Eastern cooperative oncology group (ECOG) performance status of 0 to 1 Signed informed consent document on file Females with childbearing potential must have a negative serum pregnancy Adequate organ function to receive esophagectomy including the following: Bone marrow: absolute white blood cells count ≥3.0×10^9/L, absolute neutrophil count (ANC) ≥1.5×10^9/L, platelets ≥100×10^9/L, haemoglobin ≥90g/L; Hepatic: total bilirubin ≤1.5 times upper limit of normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) ≤2.5 times ULN; Renal: calculated creatinine clearance rate≥80ml/min For childbearing potential males and females, who have agreed with contraception from start of investigational drug administration to 6 months after last dose of investigational drug Patients who have no contraindication of nab-paclitaxel, cisplatin or capecitabine Exclusion Criteria: Patients who may develop tracheoesophageal fistula or aortoesophageal fistula Patients who have received allogeneic organ or stem cell transplants Patients with uncontrolled diabetes mellitus, any serious or unstable medical condition or mental illness Patients with preexisting or a history of ≥ Grade II peripheral neuropathy Pregnant or breast feeding Patients who take part in clinical trials of other drugs or biological therapy within 4 weeks before enrollment Prior invasive malignancy in 5 years (except for curable carcinoma in situ of cervix and non-melanoma skin cancer) Patients with digestive tract obstruction or metabolic dysfunction which may influence oral absorption of capecitabine Patients with supraclavicular lymph node metastasis, celiac lymph node metastasis except for pericardial and left gastric lymph node metastasis Patients with evidence of distant metastases

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant chemotherapy group<br>Total 6 perioperative chemotherapy composed of nab-paclitaxel, cisplatin and capecitabine every 21 days | Drug: nab-paclitaxel<br>* 125mg/m2 ivgtt d1、d8<br>Drug: Cisplatin<br>* 60mg/m2 ivgtt d1 or d1-2<br>Drug: Capecitabine<br>* 1750mg/m2 po bid d1-14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR) rate | No cancer cells in primary tumor and all lymph nodes resected are observed by pathologists | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate is defined as the rate of patients with at least a 30% decrease in the sum of the LD (longest diameter) of target lesions, which include complete response (CR) or partial response (PR) | 2 year | 
| R0 resection rate | The ratio of the patients with surgical R0 resection over the of patients who receive surgery | 2 year | 
| Major Pathological Response (MPR) rate | MPR is defined as 10% or fewer viable cancer cells in the hematoxylin and eosin (H&E)-stained slides from the resected tumor following neoadjuvant treatment | 2 year | 
| Overall survival (OS) | Time from enrollment to death | From date of enrollment until the date of death from any cause, assessed up to 24 months | 
| Disease free survival (DFS) | From the day of surgery with R0 resection to recurrence or death of any reasons | From date of enrollment until the date of death or recurrence, assessed up to 24 months | 
| Progression-free survival (PFS) | number of participant with disease progression | From date of enrolment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Recurrence rate | number of participant with disease recurrence | 2 year | 
| Treatment-emergent adverse events | From the day of neoadjuvant therapy to 30 days after surgery or within 90 days after last neoadjuvant treatment. To evaluate the incidence of TEAE, rate of grade 3 and 4 TEAE (CTCAE 5.0), rate of surgery delay over 30 days and/or inoperable patients | 2 year | 
| Surgical complications |  | Within the first 90 days after the start of surgery |