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

Esophageal Squamous Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04568200
• Other study ID #: 69152630
• Status: Completed
• Phase: Phase 2
• Start date: June 19, 2020
• Est. completion date: January 1, 2024

Study information

• Verified date: January 2024
• Source: Peking Union Medical College Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: January 1, 2024
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

Drug:
• Durvalumab
Durvalumab 1500mg i.v. day 1-22-43-64
• Carboplatin
Chemotherapy
• Paclitaxel
Chemotherapy

Radiation:
• Radiotherapy 23 x 1.8 Gy
Radiotherapy 23 x 1.8 Gy

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	tumor response	assess the tumor response (by irRECIST) of preoperative treatment with durvalumab combined with neoadjuvant therapy	up to 12 months
Primary	pathological response	assess the pathological response (by CAP classification) of preoperative treatment with durvalumab combined with neoadjuvant therapy	up to 12 months
Secondary	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
Secondary	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
Secondary	Percentage completion of chemotherapy with/without radiation treatment	Percentage completion of chemotherapy with/without radiation treatment	up to 3 months
Secondary	Percentage withdrawal rate from surgery due to durvalumab related complications	Percentage withdrawal rate from surgery due to durvalumab related complications	up to 3 months
Secondary	Percentage delay of surgery due to durvalumab related complications	Percentage delay of surgery due to durvalumab related complications	up to 3 months
Secondary	R0 resection rate	R0 resection rate	up to 3 months
Secondary	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
Secondary	Progression free survival	Progression free survival	up to 24 months
Secondary	Overall survival	Overall survival	up to 24 months