Neoadjuvant Pembrolizumab Plus Chemotherapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

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

This is a study to evaluate the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy in resectable locally advanced esophageal squamous cell carcinoma patients

Study Overview

• Status: Completed
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Carboplatin or Cisplatin; Drug: Docetaxel

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Li Li, MD; Phone Number: +86-13801019675; Email: lili4037@pumch.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• 18≤Age.
• Tumor does not involve gastro-esophageal junction.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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 1.
• 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.
• Dementia or altered mental status that would prohibit the understanding and giving of informed consent
• Serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine.
• Has an active infection requiring systemic therapy which has not resolved 3 days (simple infection such as cystitis) to 7 days (severe infection such as pyelonephritis) prior to the first dose of trial treatment.
• Has a diagnosis of acute or chronic hepatitis B, hepatitis C, known immunodeficiency or human immunodeficiency virus (HIV).
• Patients with prior allogeneic stem cell or solid organ transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant Pembrolizumab Plus Chemotherapy	Drug: Pembrolizumab; Pembrolizumab 200mg i.v. day 1-22-43-64; Drug: Carboplatin or Cisplatin; Carboplatin Area Under the Curve(AUC) = 4-5 i.v. day 1-22-43-64 or Cisplatin 75mg/m2 i.v. day 1-22-43-64; Other Names: chemotherapy; Drug: Docetaxel; 75mg/m2 i.v. day 1-22-43-64; Other Names: chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor response	assess the tumor response (by irRECIST) of neoadjuvant pembrolizumab plus chemotherapy	up to 12 months
pathological response	assess the pathological responses (by College of American Pathologists(CAP) classification) of neoadjuvant pembrolizumab plus chemotherapy	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of toxicity	Incidence and severity of toxicity defined to CTCAE v4.03 and Radiation Oncology Group (RTOG) criteria	up to 12 months
R0 resection rate	R0 resection rate	up to 3 months
Overall survival	Overall survival	up to 24 months
Percentage completion of treatment	Percentage completion of treatment in neoadjuvant pembrolizumab plus chemotherapy	up to 3 months
Percentage withdrawal rate from surgery	Percentage withdrawal rate from surgery due to neoadjuvant related complications	up to 3 months
Percentage delay of surgery	Percentage delay of surgery due to neoadjuvant related complications	up to 3 months
Incidence and severity of post-operative complications to the Clavien-Dindo classification	Incidence and severity of post-operative complications to the Clavien-Dindo classification	up to 3 months
Disease free survival	Disease free survival	up to 24 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Study Chair: Li Li, MD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): March 30, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 8, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Docetaxel; Carboplatin; Pembrolizumab
• Other Study ID Numbers: Keypoint-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No