Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Resectable Esophageal Squamous Cell Carcinoma
- Conditions
- Esophageal Squamous Cell Carcinoma
- Interventions
- Registration Number
- NCT04568200
- Lead Sponsor
- Peking Union Medical College Hospital
- Brief Summary
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.
- 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. \[ Time Frame: up to 24 months \]
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description durvalumab and neoadjuvant therapy Radiotherapy 23 x 1.8 Gy 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 normal saline and neoadjuvant therapy Radiotherapy 23 x 1.8 Gy 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 durvalumab and neoadjuvant therapy Carboplatin 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 durvalumab and neoadjuvant therapy Durvalumab 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 durvalumab and neoadjuvant therapy Paclitaxel 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 normal saline and neoadjuvant therapy Carboplatin 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 normal saline and neoadjuvant therapy Paclitaxel 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
- Primary Outcome Measures
Name Time Method pathological response up to 12 months assess the pathological response (by CAP classification) of preoperative treatment with durvalumab combined with neoadjuvant therapy
tumor response up to 12 months assess the tumor response (by irRECIST) of preoperative treatment with durvalumab combined with neoadjuvant therapy
- Secondary Outcome Measures
Name Time Method Percentage withdrawal rate from surgery due to durvalumab related complications up to 3 months Percentage withdrawal rate from surgery due to durvalumab related complications
Percentage completion of treatment with durvalumab combined with chemotherapy with/without radiation treatment up to 3 months Percentage completion of treatment with durvalumab combined with chemotherapy with/without radiation treatment
Percentage completion of chemotherapy with/without radiation treatment up to 3 months Percentage completion of chemotherapy with/without radiation treatment
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 delay of surgery due to durvalumab related complications up to 3 months Percentage delay of surgery due to durvalumab related complications
R0 resection rate up to 3 months R0 resection rate
Incidence and severity of post-operative complications to the Dindo classification up to 3 months Incidence and severity of post-operative complications to the Dindo classification
Progression free survival up to 24 months Progression free survival
Overall survival up to 24 months Overall survival
Trial Locations
- Locations (1)
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China