A Phase II Trial Evaluating the Effectiveness of Itraconazole in Improving Pathologic Complete Response Rates in Patients With Esophageal Cancer Through Inhibition of the Hedgehog and AKT Signaling Pathways
Dallas VA Medical Center
Summary
Esophageal cancer, which has a low 5-year overall survival rate for all stages (\<20%) , is increasing in incidence. Previous studies have shown that the Hedgehog (Hh) and AKT signaling pathways are activated in a significant proportion of esophageal cancers. Itraconazole, a widely used anti-fungal medication, has been shown to inhibit various pathways involved in esophageal cancer tumorigenesis including Hh and AKT. In this phase II clinical trial, the investigators aim to evaluate the effect of itraconazole as a neoadjuvant therapy following standard of care chemoradiation in the treatment of locoregional esophageal and gastroesophageal junction carcinomas.
Description
Esophageal cancer has a high incidence rate in the United States, and novel approaches to its treatment are being studied. Itraconazole, an antifungal agent, has been shown to inhibit the Hedgehog (Hh) and AKT signaling pathways, which are upregulated in esophageal cancer and promote tumor cell growth. This study will evaluate whether the use of itraconazole leads to increased rates of pathological complete response (pathCR) by at least 15% from the historical pathCR rate of 25% in patients with esophageal cancer or gastroesophageal junction (GEJ) adenocarcinoma. The investigators will enroll…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients diagnosed with localized (locoregional) esophageal cancer * Patients diagnosed with localized (locoregional) gastroesophageal junction cancer Exclusion Criteria: * Patients unwilling or unable to provide informed consent * Patients with QTc\>450ms * Patients with a history of symptomatic congestive heart failure * Patients with LFT's\>3xULN * Patients who are pregnant * Patients with a known allergy to itraconazole
Interventions
- DrugItraconazole
Oral administration of itraconazole twice daily from completion of neoadjuvant chemoradiation until esophagectomy.
Location
- Dallas VA Medical CenterDallas, Texas