Clinical trial NCT05302011: Neoadjuvant Pembrolizumab Plus Chemotherapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2022-03-31
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.
* 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.

Primary outcomes:
measure: tumor response
timeFrame: up to 12 months
measure: pathological response
timeFrame: up to 12 months
Secondary outcomes:
measure: Percentage completion of treatment
timeFrame: up to 3 months
measure: Incidence and severity of toxicity
timeFrame: up to 12 months
measure: Percentage withdrawal rate from surgery
timeFrame: up to 3 months
measure: Percentage delay of surgery
timeFrame: up to 3 months
measure: R0 resection rate
timeFrame: up to 3 months
measure: Incidence and severity of post-operative complications to the Clavien-Dindo classification
timeFrame: up to 3 months
measure: Disease free survival
timeFrame: up to 24 months
measure: Overall survival
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Li Li, MD
role: STUDY_CHAIR
References: