Clinical trial NCT04568200: Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Resectable Esophageal Squamous Cell Carcinoma
Official title: 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
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: 2020-09-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. \[ Time Frame: up to 24 months \]

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),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.

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 with durvalumab combined with chemotherapy with/without radiation treatment
timeFrame: up to 3 months
measure: Incidence and severity of toxicity
timeFrame: up to 12 months
measure: Percentage completion of chemotherapy with/without radiation treatment
timeFrame: up to 3 months
measure: Percentage withdrawal rate from surgery due to durvalumab related complications
timeFrame: up to 3 months
measure: Percentage delay of surgery due to durvalumab related complications
timeFrame: up to 3 months
measure: R0 resection rate
timeFrame: up to 3 months
measure: Incidence and severity of post-operative complications to the Dindo classification
timeFrame: up to 3 months
measure: Progression 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: Jia He, MD
role: STUDY_CHAIR
References: