CCRT With Itraconazole in Locally Advanced Squamous Esophageal Cancer

Study Overview
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Brief Summary
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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

Detailed Description
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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

Official Title
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Phase II Study of Concurrent Chemoradiotherapy With Itraconazole in Treating Patients With Locally Advanced Esophageal Squamous Cancer

Conditions
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Esophageal Neoplasm, Esophageal Diseases, Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: itraconazole


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>Itraconazole capsule 100mg twice daily for 6 weeks concurrent with chemoradation. | Drug: itraconazole<br>* Oral administration of itraconazole twice daily concurrent with chemoradiation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | ORR was evaluated 4-8 weeks after completion of RT and was recorded according to RECIST, version 1.1 | 4-8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent adverse events | Incidence of treatment-emergent adverse events would be assessed based on the common toxicity criteria for adverse events version 4.0 (CTCAE v4.0) and EORTC criterion. | year 0 - year 1 | 
| Local-regional free survival (LRFS) | LRFS was calculated from the date of treatment initiation to the date of documented failure. | year 0 - year 3 | 
| Overall survival (OS) | OS was determined as the time (in months) between the first day of therapy and the last follow-up or the date of death. | year 0 - year 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophageal Squamous Cell Carcinoma, Concurrent chemoradiotherapy, Itraconazole, Hedgehog pathway