Evaluating the Effect of Itraconazole on Pathologic Complete Response Rates in Esophageal Cancer
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|ClinicalTrials.gov Identifier: NCT04018872|
Recruitment Status : Recruiting
First Posted : July 15, 2019
Last Update Posted : July 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Esophagus Adenocarcinoma Esophagus Squamous Cell Carcinoma Gastroesophageal Junction Adenocarcinoma||Drug: Itraconazole||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||78 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||June 24, 2019|
|Estimated Primary Completion Date :||June 24, 2022|
|Estimated Study Completion Date :||September 29, 2022|
Itraconazole capsule 300mg twice daily for 6-8 weeks following chemoradation.
Oral administration of itraconazole twice daily from completion of neoadjuvant chemoradiation until esophagectomy.
- Percentage of pathological complete response with itraconazole [ Time Frame: 3-4 months ]Generally for esophageal cancer the pathological complete response rate at time of esophagectomy is 25%, and we have designed our study with the projected number of patients assuming we observe an improvement of 15% or more in this rate following treatment with itraconazole. This is the study's primary endpoint. By inhibiting the Hh signaling pathway with the use of itraconazole, we anticipate improved pathological complete response rates.
- Comparison of hedgehog biomarkers before and after intervention [ Time Frame: 3-4 months ]As part of clinical staging, patients will undergo endoscopic ultrasound (EUS) following a PET/CT that does not show metastases. During EUS, some patients will undergo eight research biopsies obtained with large forceps for research purposes at the level of the visualized esophageal mass or abnormality (3 for RNA isolation, 3 for protein isolation, and 2 for formalin fixation). Three research biopsies for RNA isolation will also be obtained from normal appearing esophagus, at least 5 cm away from any mass lesions. The research biopsies will be submitted to qPCR analysis for mRNA expression levels of SHH, IHH, PTCH, GLI1, GLI2, and GLI3 (Hedgehog pathway components). Comparisons will be made between mass biopsies and normal esophageal tissues. Following esophagectomy, tissues will be analyzed for the aforementioned hedgehog pathway markers to determine response to therapy.
- Comparison of phosphorylated VEGFR2 and AKT before and after intervention [ Time Frame: 3-4 months ]Tissue obtained prior to initiation of chemoradiation will be analyzed with Western blot to quantify presence of VEGFR2 and AKT. These markers will again be analyzed following esophagectomy to determine response to therapy.
- Levels of itraconazole and metabolites in esophageal tissue [ Time Frame: 1 month. ]The concentration of itraconazole and hydroxy-itraconazole in normal esophageal tissue will be measured following esophagectomy to ensure that the drug has been taken consistently.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04018872
|Contact: David Wang, MD, PhDfirstname.lastname@example.org|
|Contact: Thai Pham, MDemail@example.com|
|United States, Texas|
|Dallas VA Medical Center||Recruiting|
|Dallas, Texas, United States, 75216|
|Contact: Jessica Vallejo, BSA|
|Contact 214-857-4237 firstname.lastname@example.org|
|Principal Investigator:||David Wang, MD, PhD||North Texas Veterans Healthcare System|