A Prospective, Single-armed Study to Evaluate the Efficacy and Safety of Neoadjuvant Pembrolizumab Plus Chemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma Patients
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Esophageal Squamous Cell Carcinoma
- Sponsor
- Peking Union Medical College Hospital
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- tumor response
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a study to evaluate the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy in resectable locally advanced esophageal squamous cell carcinoma patients
Detailed Description
The primary objective of the study is to assess the tumor response (by irRECIST) and pathological response of neoadjuvant pembrolizumab plus chemotherapy (carboplatin, paclitaxel). Secondary objectives are: To assess completion of neoadjuvant pembrolizumab plus chemotherapy. To assess toxicities of neoadjuvant pembrolizumab plus chemotherapy To assess completion of neoadjuvant pembrolizumab plus chemotherapy. To assess withdrawal rate from surgery. To assess delay rate from surgery. To assess R0 resection rate. To assess post-operative complications. Progression Free Survival.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically proven squamous cell carcinoma of the esophagus.
- •Surgical resectable (T3 or T4b, N0 or N+, M0), as determined by Endoscopic Ultra Sound (EUS),Positron Emission Tomography/Computed Tomography (PET/CT), Esophageal MRI and enhanced CT scan of neck, thorax and abdomen.
- •Tumor length longitudinal ≤ 10 cm; if larger than 10 cm, inclusion should be discussed with the principal investigator.
- •Tumor does not involve gastro-esophageal junction.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate hematological, renal and hepatic functions defined as:
- •neutrophiles ≥ 1.5 x 109/L platelets ≥ 100 x 109/L alanine transaminase≤2 x upper normal limit hemoglobin ≥ 5.6 mmol total bilirubin ≤ 1.5 x upper normal limit creatinine clearance (Cockcroft) ≥60 ml/min
- •Written, voluntary informed consent
Exclusion Criteria
- •Past or current history of malignancy other than entry diagnosis interfering with prognosis of esophageal cancer.
- •T1, T2 tumors or in situ carcinoma.
- •metastatic oesophageal cancer.
- •Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation.
- •Previous chemotherapy, radiotherapy, and/or treatment with checkpoint inhibitors.
- •Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery.
- •Pulmonary fibrosis and/or severely impaired lung function precluding major surgery.
- •Pre-existing motor or sensory neurotoxicity greater than World Health Organization (WHO) grade
- •Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (\>10 mg/day prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
Arms & Interventions
Neoadjuvant Pembrolizumab Plus Chemotherapy
Neoadjuvant Pembrolizumab Plus Chemotherapy
Intervention: Pembrolizumab
Neoadjuvant Pembrolizumab Plus Chemotherapy
Neoadjuvant Pembrolizumab Plus Chemotherapy
Intervention: Carboplatin or Cisplatin
Neoadjuvant Pembrolizumab Plus Chemotherapy
Neoadjuvant Pembrolizumab Plus Chemotherapy
Intervention: Docetaxel
Outcomes
Primary Outcomes
tumor response
Time Frame: up to 12 months
assess the tumor response (by irRECIST) of neoadjuvant pembrolizumab plus chemotherapy
pathological response
Time Frame: up to 12 months
assess the pathological responses (by College of American Pathologists(CAP) classification) of neoadjuvant pembrolizumab plus chemotherapy
Secondary Outcomes
- R0 resection rate(up to 3 months)
- Percentage completion of treatment(up to 3 months)
- Disease free survival(up to 24 months)
- Incidence and severity of toxicity(up to 12 months)
- Percentage withdrawal rate from surgery(up to 3 months)
- Percentage delay of surgery(up to 3 months)
- Incidence and severity of post-operative complications to the Clavien-Dindo classification(up to 3 months)
- Overall survival(up to 24 months)