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

NCT04568200 | Completed Phase 2

• 1 other identifier: 69152630
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Percentage completion of treatment with durvalumab combined with chemotherapy with/without radiation treatment

  up to 3 months

• Incidence and severity of toxicity

  up to 12 months

• Percentage completion of chemotherapy with/without radiation treatment

  up to 3 months

• Percentage withdrawal rate from surgery due to durvalumab related complications

  up to 3 months

• Percentage delay of surgery due to durvalumab related complications

  up to 3 months

Study Arms (2)

durvalumab and neoadjuvant therapy

EXPERIMENTAL

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

normal saline and neoadjuvant therapy

PLACEBO COMPARATOR

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

Interventions

Durvalumab DRUG

Durvalumab 1500mg i.v. day 1-22-43-64

durvalumab and neoadjuvant therapy

Carboplatin DRUG

Chemotherapy

Also known as: Chemotherapy

durvalumab and neoadjuvant therapy; normal saline and neoadjuvant therapy

Paclitaxel DRUG

Chemotherapy

Also known as: Chemotherapy

durvalumab and neoadjuvant therapy; normal saline and neoadjuvant therapy

Radiotherapy 23 x 1.8 Gy RADIATION

Radiotherapy 23 x 1.8 Gy

Also known as: Radiotherapy

durvalumab and neoadjuvant therapy; normal saline and neoadjuvant therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ≤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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

durvalumab; Carboplatin; Drug Therapy; Paclitaxel; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Jia He, MD

  Peking Union Medical College Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: September 29, 2020
• Study Start: June 19, 2020
• Primary Completion: December 1, 2023
• Study Completion: January 1, 2024
• Last Updated: January 22, 2024

Record last verified: 2024-01

Locations

CN (1)