Itraconazole in Combination With Ablation for the Prevention of Esophageal Cancer in Patients With High-risk Barrett's Esophagus
- Conditions
- Interventions
- Registration Number
- NCT06732388
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II trial tests how well itraconazole works in combination with standard of care endoscopy with ablation for the prevention of esophageal cancer in patients with high-risk Barrett's esophagus (BE). BE is a condition in which the lining of the esophagus changes. The tissue that lines the esophagus becomes more like the tissue that lines the intestin...
- Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate if itraconazole in the peri-ablation period in participants with high-risk Barrett's esophagus (BE) can accelerate BE regression i.e., achieve complete resolution of intestinal metaplasia (CRIM) faster than the control group.
SECONDARY OBJECTIVES:
...
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 64
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Participants with history of prior esophagogastroduodenoscopy (EGD) with an established diagnosis of BE ≥ 2 cm with either low-grade dysplasia (LGD) or high-grade dysplasia (HGD) or T1a esophageal adenocarcinoma (EAC), naïve to treatment, and being considered for ablation.
- Note: An eligible diagnosis from an EGD outside of the enrollment sites is allowed for inclusion as long as the biopsies have been reviewed by two pathologists. The two pathologists could include a pathologist from the referring site and an institutional pathologist at the local enrolling site, two pathologists from the referring site, or two pathologists from the local enrolling site. The diagnosis between two pathologists has to be concordant regarding the presence of dysplasia or cancer. Discrepant diagnoses will be resolved by a third pathologist, if needed
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Participants older than 18 years will be enrolled. Because the incidence of BE and related cancer is very low in participants < 18 years of age, children are excluded from this study
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Clinically eligible for EGD and endoscopic treatment of BE
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Absolute neutrophil count ≥ 1,000/microliter
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Platelets ≥ 100,000/microliter
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Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
- Note: Higher total bilirubin levels (≤ 3 mg/dL) can be allowed if due to known benign liver condition, i.e. Gilbert's
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Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) ≤ 1.5 × institutional upper limit of normal
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Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
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For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
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Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
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Participants on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible
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There are no controlled data on the effects of itraconazole on the developing human fetus at the recommended therapeutic dose. For this reason and because azoles are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) two months prior to study entry, for the duration of study participation and two months after completing the study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
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Ability to understand and the willingness to sign a written informed consent document
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Current New York Heart Association (NYHA) class III or IV congestive heart failure
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Prolonged corrected QT (QTc) (> 450 ms for men and > 470 ms for women)
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Participants may not be receiving any other investigational agents
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History of allergic reactions attributed to compounds of similar chemical or biologic composition to itraconazole
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Uncontrolled intercurrent illness., or psychiatric illness/social situations that would limit compliance with study requirements
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Pregnant women are excluded from this study because itraconazole is a class C agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with itraconazole, breastfeeding should be discontinued if the mother is treated with itraconazole
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Critical drug interactions (grades D or higher) with other medications metabolized by cytochrome P450(CYP)3A4 (if the medication cannot be discontinued or switched or dose modified); these decisions will be made on a case-by-case basis by the site investigators in consultation with the treating provider. Drug interactions can be assessed using one of the available on-line resources, for instance, UpToDate or Clinical Formulary and/or in collaboration with a clinical pharmacist.
- Note: If there are potential drug interactions that do not exclude the participant from the study, a brief research note summarizing the decision-making process about potential drug interactions and their management will be required before the participants are enrolled in the trial
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History of eosinophilic esophagitis
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History of strictures not allowing passage of the radiofrequency ablation (RFA) assembly
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Participants must not have evidence of active/recurrent invasive cancer of a non-esophageal organ
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Participants with EAC greater than stage T1a
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (itraconazole) Biopsy Patients receive itraconazole PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. Arm I (itraconazole) Endoscopic Procedure Patients receive itraconazole PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. Arm II (placebo) Biospecimen Collection Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. Arm I (itraconazole) Biospecimen Collection Patients receive itraconazole PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. Arm I (itraconazole) Itraconazole Patients receive itraconazole PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. Arm I (itraconazole) Questionnaire Administration Patients receive itraconazole PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. Arm I (itraconazole) Radiofrequency Ablation Patients receive itraconazole PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. Arm II (placebo) Biopsy Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. Arm II (placebo) Endoscopic Procedure Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. Arm II (placebo) Placebo Administration Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. Arm II (placebo) Questionnaire Administration Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study. Arm II (placebo) Radiofrequency Ablation Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo standard of care endoscopy and radiofrequency ablation on study. Patients also undergo blood sample collection throughout the study as well as tissue biopsy on study.
- Primary Outcome Measures
Name Time Method Time to complete resolution of intestinal metaplasia (CRIM) in days Between day 1, cycle 1 (1 cycle = 6 weeks) and the date of endoscopy at which the participant is deemed to reach CRIM CRIM will be defined based on the absence of visible Barrett's esophagus (BE) and invisible BE (i.e., no intestinal metaplasia \[IM\] in biopsies of the gastroesophageal junction and the cardia). Will be reported descriptively. Will compare the unadjusted hazard rates between the itraconazole and control groups using log rank test.
- Secondary Outcome Measures
Name Time Method Time to complete eradication of dysplasia Between day 1, cycle 1 (1 cycle = 6 weeks) and the date of endoscopy at which surveillance biopsies do not show dysplasia Will be assessed by surveillance biopsies at the time of the endoscopy that documents CRIM and the biopsies at the time of first surveillance endoscopy will be evaluated for dysplasia.
Rate of BE recurrence over follow-up At 12 months after CRIM Will be assessed between the study treatment group and the control group. BE recurrence will be defined as histologic presence of IM (with or without dysplasia) in biopsies from the tubular esophagus or in biopsies at the gastroesophageal junction. The results from the standrd of care endoscopy closest to the 12-month time point after CRIM will be used to co...
Incidence of adverse events Up to 30 days after the end of intervention Will be assessed by National Cancer Institutes Common Terminology Criteria for Adverse Events version 5.0 criteria to document adverse events and measure specific laboratory parameters to monitor for the safety and tolerability of itraconazole and assessed by descriptive statistics.
Correlate levels of itraconazole and its primary metabolite hydroxyitraconazole After two weeks of itraconazole Will be assessed in plasma and esophageal tissues with treatment response. Will measure these metabolites after two weeks of itraconazole therapy by obtaining biopsies of the esophagus. These measurements will be correlated with biomarker and clinical response to understand how tissue levels of the drug change the molecular and primary endpoints. Will also m...
Biosocial impact At baseline and at the end of the study Will be assessed by questionnaires to collect information about the biosocial endpoints. These will include cancer-specific distress questionnaire, Gastrointestinal Symptom Rating Scale, Health-Related Quality of life short form 12 version 2, and Patient-Reported Outcomes Measurement Information System anxiety and depression scores as previously used at the ...
Trial Locations
- Locations (7)
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States