3-AP Plus Cisplatin in Treating Patients With Recurrent or Metastatic Adenocarcinoma of the Esophagus or Gastroesophageal Junction

Study Overview
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Brief Summary
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Drugs used in chemotherapy, such as 3-AP and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. 3-AP may help cisplatin kill more cancer cells by making them more sensitive to the drug. This phase II trial is studying how well giving 3-AP together with cisplatin works in treating patients with recurrent or metastatic adenocarcinoma of the esophagus or gastroesophageal junction.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the objective response rate in patients with recurrent or metastatic adenocarcinoma of the esophagus or gastroesophageal junction treated with 3-AP (Triapine) and cisplatin. SECONDARY OBJECTIVES: I. Determine the toxicity of this regimen in these patients. II. Determine the duration of response and overall survival of patients treated with this regimen. III. Determine the palliative benefits with regard to dysphagia in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive 3-AP (Triapine) IV over 2 hours on days 1-4. Patients also receive cisplatin IV over 60 minutes on days 2 and 3 before 3-AP infusion. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed for up to 2 years. PROJECTED ACCRUAL: A total of 19-39 patients will be accrued for this study within 20 months.

Official Title
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A Phase II Study Of Triapine In Combination With Cisplatin Esophageal Carcinoma

Conditions
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Adenocarcinoma of the Esophagus, Recurrent Esophageal Cancer, Stage IV Esophageal Cancer

Intervention / Treatment
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* Drug: triapine
* Drug: cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction Metastatic or recurrent disease Measurable disease At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Outside prior irradiation port No known brain metastases Performance status - ECOG 0-2 Performance status - Karnofsky 50-100% More than 6 months Absolute neutrophil count ≥ 1,500/mm^3 WBC ≥ 3,000/mm ^3 Platelet count ≥ 100,000/mm^3 AST and ALT ≤ 2.5 times upper limit of normal Bilirubin normal Creatine normal Creatinine clearance ≥ 50 mL/min No prior myocardial infarction No unstable angina No cardiac arrhythmia No uncontrolled congestive heart failure No pulmonary disease requiring supplemental oxygen Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation No glucose-6-phosphate dehydrogenase (G6PD) deficiency (for patients of African, Asian, or Mediterranean origin) No other concurrent uncontrolled illness No active or ongoing infection No active second malignancy No prior allergic reaction to compounds of similar chemical or biological composition to 3-AP or other study agents No psychiatric illness or social situation that would preclude study compliance At least 1 year since prior platinum-derivative agents No prior chemotherapy for metastatic or recurrent esophageal cancer See Disease Characteristics At least 2 weeks since prior radiotherapy and recovered No other concurrent anticancer therapy No other concurrent investigational agents No concurrent combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (triapine and cisplatin)<br>Patients receive 3-AP (Triapine) IV over 2 hours on days 1-4. Patients also receive cisplatin IV over 60 minutes on days 2 and 3 before 3-AP infusion. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Drug: triapine<br>* Given IV<br>Drug: cisplatin<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate | Will be calculated together with 95% confidence intervals based on the binomial distribution. | Up to 2 years | 
| Objective response rate (CR + PR) | Will be calculated together with 95% confidence intervals based on the binomial distribution. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Kaplan-Meier estimates will be determined. | Up to 2 years | 
| Progression-free survival | Kaplan-Meier estimates will be determined. | From the start of treatment to progression or death, assessed up to 2 years | 
| Duration of response |  | From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years | 
| Number of patients with various treatment-related toxicities assessed using NCI CTCAE version 3.0 |  | Up to 2 years | 
| Number of patients with improvement of dysphagia |  | Up to 2 years | 
| Duration of improvement of dysphagia |  | Up to 2 years |