CCRT With Itraconazole in Locally Advanced Squamous Esophageal Cancer

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

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

Study Overview

• Status: Recruiting
• Conditions: Esophageal Diseases; Esophageal Squamous Cell Carcinoma; Esophageal Neoplasm
• Intervention / Treatment: Drug: itraconazole

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shixiu Wu, phD; Phone Number: 86-755-66618168; Email: wushixiu@medmail.com.cn

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518116
      • Recruiting
      • National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
      • Contact: Shixiu Wu, phD; Phone Number: +8675566618168; Email: wushixiu@medmail.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; Itraconazole capsule 100mg twice daily for 6 weeks concurrent with chemoradation.	Drug: itraconazole; Oral administration of itraconazole twice daily concurrent with chemoradiation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hangzhou Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Anticipated): July 31, 2021
• Study Completion (Anticipated): July 31, 2023

Study Registration Dates

• First Submitted: July 17, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 13, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Esophageal Squamous Cell Carcinoma; Itraconazole; Concurrent chemoradiotherapy; Hedgehog pathway
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophageal Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: 20200707

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No