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

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05302011

Collaborator

(none)

Enrollment

Location

Arm

24.9

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Esophageal Squamous Cell Carcinoma	Drug: Pembrolizumab Drug: Carboplatin or Cisplatin Drug: Docetaxel	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2020

Anticipated Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neoadjuvant Pembrolizumab Plus Chemotherapy 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

Arm

Intervention/Treatment

Experimental: Neoadjuvant Pembrolizumab Plus Chemotherapy

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

Outcome Measures

Primary Outcome Measures

tumor response [up to 12 months]
assess the tumor response (by irRECIST) of neoadjuvant pembrolizumab plus chemotherapy
pathological response [up to 12 months]
assess the pathological responses (by College of American Pathologists(CAP) classification) of neoadjuvant pembrolizumab plus chemotherapy

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.