78 Participants Needed

Itraconazole for Esophageal Cancer

Recruiting at 6 trial locations
DH
JD
Overseen ByJonathan Dowell, MD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: VA Office of Research and Development
Stay on Your Current MedsYou can continue your current medications while participating
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What evidence supports the effectiveness of the drug itraconazole for esophageal cancer?

Research shows that itraconazole, a drug usually used to treat fungal infections, can slow down the growth of esophageal cancer cells by blocking certain proteins (HER2/AKT) that help cancer cells grow. It also activates a process (AMPK signaling) that leads to cancer cell death, which has been observed in both lab studies and early clinical trials.12345

How does the drug itraconazole differ from other treatments for esophageal cancer?

Itraconazole, originally an antifungal medication, is unique in treating esophageal cancer because it works by blocking specific pathways (HER2/AKT and AMPK) that help cancer cells grow. This mechanism is different from traditional chemotherapy or radiation, which do not specifically target these pathways.13678

What is the purpose of this trial?

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.

Research Team

DH

David H Wang, MD PhD

Principal Investigator

VA Ann Arbor Healthcare System, Ann Arbor, MI

Eligibility Criteria

This trial is for individuals who can consent and have been diagnosed with resectable esophageal or gastroesophageal junction cancer, planning to undergo chemoradiation and surgery. They should be relatively active (WHO/ECOG status 0-2) and have good kidney and liver function.

Inclusion Criteria

I understand the study and can agree to participate.
I can take care of myself and perform daily activities.
My kidney and liver are working well.
See 1 more

Exclusion Criteria

My heart's electrical cycle is longer than normal and will be monitored.
Inability to provide Informed Consent
I am allergic to the medication itraconazole.
See 3 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Pre-treatment with Itraconazole

Participants receive oral itraconazole for 2 weeks before starting standard of care neoadjuvant chemoradiation

2 weeks
1 visit (in-person)

Neoadjuvant Chemoradiation

Participants undergo standard of care neoadjuvant chemoradiation

6-8 weeks
Weekly visits (in-person)

Post-chemoradiation with Itraconazole

Participants receive oral itraconazole for 6-8 weeks after completion of chemoradiation

6-8 weeks
Bi-weekly visits (in-person)

Surgery

Participants undergo esophagectomy if no new metastases are found

1 week
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
2 visits (in-person)

Treatment Details

Interventions

  • Itraconazole
Trial Overview The trial tests Itraconazole as an add-on to standard care in treating locoregional esophageal cancers. It's a phase II study, meaning it focuses on the drug's effectiveness when combined with chemotherapy, radiation therapy, and surgery.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: ItraconazoleExperimental Treatment1 Intervention
Itraconazole 300 mg po bid for two weeks prior and 6-8 weeks after completion of standard of care neoadjuvant chemoradiation

Find a Clinic Near You

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials
1,691
Recruited
3,759,000+

VA Puget Sound Health Care System

Collaborator

Trials
67
Recruited
225,000+

Michael E. DeBakey VA Medical Center

Collaborator

Trials
68
Recruited
17,200+

Portland VA Medical Center

Collaborator

Trials
44
Recruited
7,800+

VA Palo Alto Health Care System

Collaborator

Trials
97
Recruited
58,500+

VA Boston Healthcare System

Collaborator

Trials
73
Recruited
971,000+

North Texas Veterans Healthcare System

Collaborator

Trials
39
Recruited
4,005,000+

VA Ann Arbor Healthcare System

Collaborator

Trials
19
Recruited
10,300+

Durham VA Health Care System

Collaborator

Trials
8
Recruited
64,900+

Findings from Research

Itraconazole, an FDA-approved antifungal, shows significant antitumor activity against esophageal cancer by inhibiting cell proliferation and inducing cell-cycle arrest, particularly affecting esophageal squamous cell carcinoma and adenocarcinoma cell lines.
The mechanism of action involves downregulation of the HER2/AKT signaling pathway, as evidenced by decreased phosphorylation of key proteins in both cell lines and mouse xenograft models, along with promising results from an early phase I clinical trial in patients with esophageal cancer.
Itraconazole Exerts Its Antitumor Effect in Esophageal Cancer By Suppressing the HER2/AKT Signaling Pathway.Zhang, W., Bhagwath, AS., Ramzan, Z., et al.[2022]
Biologic therapies, particularly those targeting HER2 and VEGF, are showing promise in treating esophageal and gastric cancers, with trastuzumab and ramucirumab currently recommended by the NCCN for specific patient groups.
Recent studies indicate that other agents like pertuzumab, apatinib, and pembrolizumab may improve overall and progression-free survival, suggesting a growing role for targeted biologic therapies in clinical practice.
Biologic therapy in esophageal and gastric malignancies: current therapies and future directions.Samson, P., Lockhart, AC.[2020]
Itraconazole, an antifungal drug, effectively inhibits the growth and survival of esophageal cancer cells by activating AMPK signaling, which is crucial for inducing cell death.
In vivo studies demonstrated that itraconazole significantly reduced tumor growth in mice, but this effect was lost when AMPK signaling was inhibited, highlighting the importance of AMPK in its mechanism of action against esophageal cancer.
Itraconazole-Induced Inhibition on Human Esophageal Cancer Cell Growth Requires AMPK Activation.Chen, MB., Liu, YY., Xing, ZY., et al.[2020]

References

Itraconazole Exerts Its Antitumor Effect in Esophageal Cancer By Suppressing the HER2/AKT Signaling Pathway. [2022]
Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]
Itraconazole-Induced Inhibition on Human Esophageal Cancer Cell Growth Requires AMPK Activation. [2020]
A randomised trial of radiotherapy compared with cisplatin chemo-radiotherapy in patients with unresectable squamous cell cancer of the esophagus. [2013]
[Clinical efficacy of anlotinib plus S-1 as a second-line therapy for recurrent or metastatic esophageal squamous cell carcinoma]. [2021]
Long-Term Results of a Phase 2 Study of Definitive Chemoradiation Therapy Using S-1 for Esophageal Squamous Cell Carcinoma Patients Who Were Elderly or With Serious Comorbidities. [2022]
Neoadjuvant chemotherapy and surgery of cancer of the esophagus. [2019]
Neoadjuvant chemotherapy and surgery of cancer of the esophagus. [2019]
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Back to top
Terms of Service·Privacy Policy·Cookies·Security