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

Esophageal Squamous Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05302011
• Other study ID #: Keypoint-1
• Status: Completed
• Phase: Phase 2
• Start date: June 1, 2020
• Est. completion date: June 30, 2023

Study information

• Verified date: October 2023
• Source: Peking Union Medical College Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: June 30, 2023
• Est. primary completion date: March 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

Drug:
• Pembrolizumab
Pembrolizumab 200mg i.v. day 1-22-43-64
• 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
• Docetaxel
75mg/m2 i.v. day 1-22-43-64

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	tumor response	assess the tumor response (by irRECIST) of neoadjuvant pembrolizumab plus chemotherapy	up to 12 months
Primary	pathological response	assess the pathological responses (by College of American Pathologists(CAP) classification) of neoadjuvant pembrolizumab plus chemotherapy	up to 12 months
Secondary	Percentage completion of treatment	Percentage completion of treatment in neoadjuvant pembrolizumab plus chemotherapy	up to 3 months
Secondary	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
Secondary	Percentage withdrawal rate from surgery	Percentage withdrawal rate from surgery due to neoadjuvant related complications	up to 3 months
Secondary	Percentage delay of surgery	Percentage delay of surgery due to neoadjuvant related complications	up to 3 months
Secondary	R0 resection rate	R0 resection rate	up to 3 months
Secondary	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
Secondary	Disease free survival	Disease free survival	up to 24 months
Secondary	Overall survival	Overall survival	up to 24 months