Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Resectable Esophageal Squamous Cell Carcinoma

A Prospective, Randomized Controlled Study to Evaluate the Efficacy and Safety of Durvalumab Combined With Neoadjuvant Therapy in Patients With Local Advanced Esophageal Squamous Cell Carcinoma

This is a study to evaluate the efficacy and safety of preoperative treatment with durvalumab combined with neoajuvant therapy (carboplatin, paclitaxel with/without radiation) in locally advanced resectable oesophageal squamous carcinoma.

Study Overview

• Status: Completed
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Paclitaxel; Drug: Carboplatin; Drug: Durvalumab; Radiation: Radiotherapy 23 x 1.8 Gy

Detailed Description

The primary objective of the study is to assess the tumor response (by irRECIST) and pathological response of preoperative treatment with durvalumab combined with neoadjuvant therapy (carboplatin, paclitaxel with/without radiation).

Secondary objectives are:

To assess completion of treatment with durvalumab combined with chemotherapy with/without radiation treatment.

To assess toxicities of durvalumab in combination with chemoradiation. [Time Frame: up to 1 year] To assess completion of chemotherapy with/without radiation treatment. 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. [ Time Frame: up to 24 months ] Overall Survival. [ Time Frame: up to 24 months ]

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jia He, MD; Phone Number: +86-13810096213; Email: hejia@126.com

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (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),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≤75.
• 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 (Cockroft) ≥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 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: durvalumab and neoadjuvant therapy; durvalumab 1500mg i.v. day 1-22-43-64 Carboplatin AUC = 4-5 i.v day 1-22-43-64 Paclitaxel 75 mg/m2 i.v day 1-22-43-64 with/without Radiotherapy 23 x 1.8 Gy	Drug: Paclitaxel; Chemotherapy; Other Names: Chemotherapy; Drug: Carboplatin; Chemotherapy; Other Names: Chemotherapy; Drug: Durvalumab; Durvalumab 1500mg i.v. day 1-22-43-64; Radiation: Radiotherapy 23 x 1.8 Gy; Radiotherapy 23 x 1.8 Gy; Other Names: Radiotherapy
Placebo Comparator: normal saline and neoadjuvant therapy; normal saline 500ml i.v. day 1-22-43-64 Carboplatin AUC = 4-5 i.v day 1-22-43-64 Paclitaxel 75 mg/m2 i.v day 1-22-43-64 with/without Radiotherapy 23 x 1.8 Gy	Drug: Paclitaxel; Chemotherapy; Other Names: Chemotherapy; Drug: Carboplatin; Chemotherapy; Other Names: Chemotherapy; Radiation: Radiotherapy 23 x 1.8 Gy; Radiotherapy 23 x 1.8 Gy; Other Names: Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor response	assess the tumor response (by irRECIST) of preoperative treatment with durvalumab combined with neoadjuvant therapy	up to 12 months
pathological response	assess the pathological response (by CAP classification) of preoperative treatment with durvalumab combined with neoadjuvant therapy	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of post-operative complications to the Dindo classification	Incidence and severity of post-operative complications to the Dindo classification	up to 3 months
Percentage completion of treatment with durvalumab combined with chemotherapy with/without radiation treatment	Percentage completion of treatment with durvalumab combined with chemotherapy with/without radiation treatment	up to 3 months
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
Percentage completion of chemotherapy with/without radiation treatment	Percentage completion of chemotherapy with/without radiation treatment	up to 3 months
Percentage withdrawal rate from surgery due to durvalumab related complications	Percentage withdrawal rate from surgery due to durvalumab related complications	up to 3 months
Percentage delay of surgery due to durvalumab related complications	Percentage delay of surgery due to durvalumab related complications	up to 3 months
R0 resection rate	R0 resection rate	up to 3 months
Progression free survival	Progression free survival	up to 24 months
Overall survival	Overall survival	up to 24 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2020
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): January 1, 2024

Study Registration Dates

• First Submitted: September 15, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 29, 2020

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

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, Phytogenic; Antineoplastic Agents, Immunological; Carboplatin; Paclitaxel; Durvalumab
• Other Study ID Numbers: 69152630

Drug and device information, study documents

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