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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Completed; Phase 2

Conditions: Esophageal Squamous Cell Carcinoma

Treatments: Drug: Carboplatin; Drug: Durvalumab; Drug: Paclitaxel; Radiation: Radiotherapy 23 x 1.8 Gy

Study type: Interventional

Funder types: Other

Identifiers

NCT04568200

69152630

Details and patient eligibility

About

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.

Full 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 ]

Enrollment: 60 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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),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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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60 participants in 2 patient groups, including a placebo group

durvalumab and neoadjuvant therapy

Experimental group

Description:

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

Treatment:

Radiation: Radiotherapy 23 x 1.8 Gy

Drug: Paclitaxel

Drug: Durvalumab

Drug: Carboplatin

normal saline and neoadjuvant therapy

Placebo Comparator group

Description:

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

Treatment:

Radiation: Radiotherapy 23 x 1.8 Gy

Drug: Paclitaxel

Drug: Carboplatin