What side effects are associated with this type of intervention?

Common treatments for Gastroesophageal Junction Adenocarcinoma, including chemoradiation and targeted therapies, often have a range of side effects. Chemoradiation can cause nausea, vomiting, esophagitis, fatigue, and myelosuppression. Targeted therapies, such as those inhibiting the Hedgehog and AKT pathways, may lead to side effects like hypertension, diarrhea, hypothyroidism, and skin reactions. Additionally, specific agents like ramucirumab can cause hypertension and increased risk of thromboembolic events. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

FDA-approved treatments for Gastroesophageal Junction (GEJ) Adenocarcinoma include targeted therapies such as trastuzumab, which is used for HER2-positive tumors, and pembrolizumab, an anti-PD-1 monoclonal antibody for PD-L1 expressing tumors. While Itraconazole, which inhibits Hedgehog and AKT signaling pathways, is under investigation, other drugs targeting similar pathways have not been specifically highlighted in the provided context. Broadly, the treatment landscape for GEJ adenocarcinoma includes chemotherapy, targeted therapy, and immunotherapy, with ongoing research into novel agents and combinations.

What other types of research exist?

Promising novel alternatives to Itraconazole for Gastroesophageal Junction Adenocarcinoma patients include: 1) Pembrolizumab plus cetuximab, which is being investigated for its efficacy in treatment-refractory metastatic head and neck cancer and may have potential applications in gastroesophageal junction adenocarcinoma. 2) Farnesyltransferase inhibitors like tipifarnib, which have shown encouraging response rates in HRAS mutant squamous cell carcinoma of the head and neck and could be explored for similar mutations in gastroesophageal junction adenocarcinoma. 3) Metronomic chemotherapy, which uses frequent, lower doses of chemotherapy to target tumor angiogenesis and minimize toxicity, remains an investigational approach that could be considered.

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Itraconazole for Esophageal Cancer

Phase 2

Recruiting

Led By David Wang, MD, PhD

Research Sponsored by Dallas VA Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients diagnosed with localized (locoregional) esophageal cancer

Patients diagnosed with localized (locoregional) gastroesophageal junction cancer

Must not have

Patients with a history of symptomatic congestive heart failure

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3-4 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if itraconazole, a drug for fungal infections, can help treat esophageal cancer. It targets patients with poor survival rates. The drug works by blocking growth signals in cancer cells. The trial will see if adding itraconazole after standard treatment improves outcomes. Itraconazole is an FDA-approved antifungal agent that has shown promising anticancer activities in recent years.

Who is the study for?

This trial is for individuals with localized esophageal or gastroesophageal junction cancer. Participants must be able to consent, have normal heart rhythm (QTc ≤450ms), no severe heart failure history, liver function tests within three times the upper limit of normal, and not be pregnant or allergic to itraconazole.

What is being tested?

The study is testing if Itraconazole can improve outcomes when given before standard chemoradiation therapy in treating esophageal and gastroesophageal junction cancers. It's a phase II trial focusing on how this anti-fungal drug affects cancer pathways.

What are the potential side effects?

Itraconazole may cause side effects like nausea, rash, liver problems, heart issues such as congestive heart failure or abnormal heartbeat (QT prolongation), and could potentially interact with other medications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My esophageal cancer has not spread beyond the local area.

Select...

My cancer is located at the junction of the stomach and esophagus.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have had heart failure symptoms in the past.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3-4 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3-4 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3-4 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of pathological complete response with itraconazole

Secondary study objectives

Comparison of hedgehog biomarkers before and after intervention

Comparison of phosphorylated VEGFR2 and AKT before and after intervention

Levels of itraconazole and metabolites in esophageal tissue

Side effects data

From 2015 Phase 1 & 2 trial • 178 Patients • NCT01974687

33%

Abnormal faeces

33%

Nausea

33%

Dizziness

17%

Dry mouth

17%

Flushing

17%

Abdominal discomfort

17%

Vomiting

17%

Headache

17%

Erythema

100%

80%

60%

40%

20%

Study treatment Arm

Group A: Uprifosbuvir 150 mg (Cohort 4a)

Group B: Uprifosbuvir 150 mg (Cohort 4b)

Group F: Uprifosbuvir 300 mg (Tablet)

Groups C & D: Uprifosbuvir 150 mg (Capsule)

Group A: Uprifosbuvir 300 mg (Cohort 6a)

Group B: Uprifosbuvir 50 mg (Cohort 3b)

Group B: Uprifosbuvir 10 mg (Cohort 1b)

Group B: Uprifosbuvir 300 mg (Cohort 5b)

Groups C & D: Uprifosbuvir 50 mg (Capsule)

Groups C & D: Uprifosbuvir 300 mg (Capsule)

Groups C & D: Uprifosbuvir 300 mg (Tablet)

Groups C & D: Uprifosbuvir 400 mg (Capsule)

Group A: Placebo (Cohort 6a)

Group B: Uprifosbuvir 25 mg (Cohort 2b)

Groups C & D: Uprifosbuvir 250 mg (Capsule)

Group A: Placebo (Cohort 1a - Cohort 5a - Pooled)

Group A: Uprifosbuvir 10 mg (Cohort 1a)

Group A: Uprifosbuvir 25 mg (Cohort 2a)

Group A: Uprifosbuvir 50 mg (Cohort 3a)

Group A: Uprifosbuvir 300 mg (Cohort 5a)

Groups C & D: Uprifosbuvir 450 mg (Tablet)

Groups C & D: Placebo (Pooled)

Group E: Uprifosbuvir 150 mg (Cohort 1e)

Group E: Uprifosbuvir 300 mg (Cohort 2e)

Group E: Uprifosbuvir 450 mg (Cohort 3e)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: ItraconazoleExperimental Treatment1 Intervention

Itraconazole capsule 300mg twice daily for 6-8 weeks following chemoradation.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Itraconazole

2017

Completed Phase 2

~830

0 / 3Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Gastroesophageal Junction (GEJ) Adenocarcinoma often target specific signaling pathways crucial for cancer growth and survival. Itraconazole, for example, inhibits the Hedgehog (Hh) and AKT pathways, which are involved in tumorigenesis. Chemoradiation, using drugs like fluorouracil and cisplatin, works by damaging DNA and inhibiting cell division. Targeted therapies, such as trastuzumab, focus on inhibiting growth signals specific to cancer cells, like HER2. Understanding these mechanisms allows for personalized treatment plans that can more effectively target the cancer's specific pathways, improving outcomes for patients.

Targeted therapies with chemoradiation in esophageal cancer: development and future directions.