The objective of this study is to evaluate the efficacy and safety of concurrent chemoradiotherapy combined with Itraconazole in patients with locally adcvanced esophageal squamous cancer

Esophageal cancer is one of the most lethal malignancies. Esophageal squamous cell carcinoma (ESCC) is the predominant type in China, accounting for over 90% of all esophageal cancer. Concurrent chemoradiation therapy (CCRT) remains the standard therapy of locally advanced ESCC. However, the outcome remains poor.

The aberrant activation of Hedgehog (HH) signaling is associated with a variety of human malignancies. Previous studies found that the reactivation of HH pathway occurs in 60% of esophageal cancer. Targeting the Hh pathway for cancer therapy was expected to work wonders in Hh-dependent cancers. Itraconazole, an antifungal agent, has been shown to inhibit the Hh and AKT signaling pathways.

The aim of our study is to evaluate the efficacy and safety of concurrent chemoradiotherapy combined with Itraconazole in patients with locally adcvanced esophageal squamous cancer

Inclusion Criteria:

age:18-75 years, male or femal.

Histologically or cytologically confirmed Squamous Cell Carcinoma of the Esophagus, locally advanced, unresectable disease.

Clinical staged T3-4N0M0, T1-4N+M0,Ⅱ-Ⅳa(AJCC 8th)

Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

ECOG 0-1.

Adequate organ function.

Patient has given written informed consent.

Exclusion Criteria:

Unwilling or unable to provide informed consent

Known allergy to itraconazole

Patients who have or are currently undergoing additional chemotherapy, radiation therapy, targeted therapy or immunotherapy.

Complete obstruction of the esophagus, or patients who have the potential to develop perforation, or unable to swallow Itraconazole.

Other malignancy within 5 years prior to entry into the study, expect for curatively treated basal cell and squamous cell carcinoma of the skin and/or curatively resected in-situ cervical and/or breast cancers.

Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent.

Pregnancy or breast-feeding.

Decision of unsuitableness by principal investigator or physician-in-charge.