Trial Title:
A Phase II Trial to Evaluate the Effect of Itraconazole on Pathologic Complete Response Rates in Resectable Esophageal Cancer
NCT ID:
NCT05563766
Condition:
Esophageal Adenocarcinoma
Esophageal Squamous Cell Carcinoma
Gastroesophageal Junction Carcinoma
Conditions: Official terms:
Carcinoma
Esophageal Neoplasms
Esophageal Squamous Cell Carcinoma
Pathologic Complete Response
Itraconazole
Conditions: Keywords:
Itraconazole
Neoadjuvant
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Single arm, patients will receive itraconazole 300 mg po bid for two weeks prior and 6-8
weeks after standard of care neoadjuvant chemoradiation.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Itraconazole
Description:
Itraconazole 300 mg po bid for two weeks prior and 6-8 weeks after completion of standard
of care neoadjuvant chemoradiation
Arm group label:
Itraconazole
Summary:
Esophageal cancer, which has a low 5-year overall survival rate (<20%) is increasing in
incidence. Previous studies have shown that Hedgehog, AKT, and angiogenic signaling
pathways are activated in a significant number of esophageal cancers. Itraconazole, a
widely used anti-fungal medication, effectively inhibits these pathways. In this
multi-site phase II trial, the investigators will evaluate the effect of itraconazole as
a neoadjuvant therapy added to standard of care chemoradiation and surgery in the the
treatment of locoregional esophageal and gastroesophageal junction cancers.
Detailed description:
Esophageal cancer has a high incidence rate in the United States, and novel approaches to
improve its treatment are being studied. Itraconazole, an antifungal agent approved by
the FDA in 1992, has been shown to inhibit the Hedgehog (Hh), AKT, and VEGFR2 signaling
pathways which are upregulated in esophageal cancer and promote tumor growth. This study
will evaluate whether the use of itraconazole leads to increased rates of pathologic
complete response (pathCR) by at least 15% compared to propensity-score matched control
patients with esophageal or gastroesophageal junction (GEJ) cancer. The investigators
will enroll 78 patients with esophageal or GEJ cancer who will undergo standard of care
staging workup with a PET/CT and endoscopic ultrasound (EUS). If no distant metastases
are found, patients will receive 2 weeks of oral itraconazole before starting standard of
care neoadjuvant chemoradiation. Upon completion of chemoradiation, patients will receive
oral itraconazole for 6-8 weeks. Adverse effects to itraconazole will be monitored and
drug levels will be obtained during clinic visits. If standard restaging PET/CT following
neoadjuvant chemoradiation does not reveal new metastases, patients will undergo
esophagectomy after consultation with their physician team. Samples from normal
esophageal tissue will be analyzed for presence of itraconazole and its metabolite to
determine if patients were compliant in taking study drug. Residual tumor tissue will be
evaluated for status of the Hh, AKT, and VEGFR2 pathways with comparisons made to
pre-treatment biopsies. The final pathology report will indicate whether the patient has
achieved pathCR. Because Hh, AKT, and angiogenic signaling pathways can be upregulated in
response to chemoradiation, the investigators believe that administering itraconazole
around chemoradiation will lead to higher pathCR rates. This in turn should be able to
improve treatment outcomes in patients with esophageal and GEJ cancer. Secondary
endpoints include correlating drug levels and molecular pathway status to pathCR,
determining a genomic profile that predicts treatment response, and evaluating ctDNA and
exosomes as additional markers of treatment response.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Capable of giving informed consent
- Pathologic diagnosis of esophageal cancer (ESCC or EAC) or GEJ cancer deemed
resectable by a surgeon with a plan to undergo neoadjuvant chemoradiation and
curative intent esophagectomy
- World Health Organization (WHO)/ECOG performance status (PS) of 0-2 at enrollment
- Adequate renal and liver function as judged by the treating physician
Exclusion Criteria:
- Inability to provide Informed Consent
- NYHA class III or IV CHF
- LFT>3X upper limit of normal
- Drug allergy to itraconazole
- Positive pregnancy test
- Those with QTc>450 ms will have QTc monitored during therapy by serial EKG to ensure
QTc does not lengthen to what the treating clinician considers significant
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
VA Palo Alto Health Care System, Palo Alto, CA
Address:
City:
Palo Alto
Zip:
94304-1290
Country:
United States
Contact:
Last name:
Albert Lin, MD
Phone:
650-493-5000
Phone ext:
69523
Email:
albert.lin6@va.gov
Facility:
Name:
VA Ann Arbor Healthcare System, Ann Arbor, MI
Address:
City:
Ann Arbor
Zip:
48105-2303
Country:
United States
Contact:
Last name:
Brittany M Pannecouk, BS
Phone:
734-845-3966
Email:
brittany.pannecouk@va.gov
Investigator:
Last name:
David H Wang, MD PhD
Email:
Principal Investigator
Facility:
Name:
Durham VA Medical Center, Durham, NC
Address:
City:
Durham
Zip:
27705
Country:
United States
Contact:
Last name:
Michael Kelley, MD
Phone:
919-286-0411
Phone ext:
172199
Email:
michael.kelley6@va.gov
Facility:
Name:
VA Portland Health Care System, Portland, OR
Address:
City:
Portland
Zip:
97239
Country:
United States
Contact:
Last name:
Kenneth Bensch, MD
Phone:
503-220-8262
Phone ext:
5594
Email:
kenneth.bensch1@va.gov
Facility:
Name:
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Address:
City:
Dallas
Zip:
75216-7167
Country:
United States
Contact:
Last name:
Nicole Pore-Brown
Phone:
214-857-3291
Email:
Florine.Pore-Brown@va.gov
Facility:
Name:
Michael E. DeBakey VA Medical Center, Houston, TX
Address:
City:
Houston
Zip:
77030
Country:
United States
Contact:
Last name:
Yvonne Sada, MD
Phone:
713-794-7454
Email:
yvonne.sada@va.gov
Facility:
Name:
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Address:
City:
Seattle
Zip:
98108
Country:
United States
Contact:
Last name:
Daniel Wu, MD
Phone:
206-764-2182
Email:
daniel.wu@va.gov
Start date:
October 1, 2024
Completion date:
June 15, 2029
Lead sponsor:
Agency:
VA Office of Research and Development
Agency class:
U.S. Fed
Collaborator:
Agency:
Durham VA Health Care System
Agency class:
U.S. Fed
Collaborator:
Agency:
VA Palo Alto Health Care System
Agency class:
U.S. Fed
Collaborator:
Agency:
Portland VA Medical Center
Agency class:
U.S. Fed
Collaborator:
Agency:
VA Puget Sound Health Care System
Agency class:
U.S. Fed
Collaborator:
Agency:
Michael E. DeBakey VA Medical Center
Agency class:
U.S. Fed
Collaborator:
Agency:
VA Boston Healthcare System
Agency class:
U.S. Fed
Source:
VA Office of Research and Development
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05563766
