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

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

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.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma of the Esophagus; Recurrent Esophageal Cancer; Stage IV Esophageal Cancer
• Intervention / Treatment: Drug: triapine; Drug: cisplatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (triapine and cisplatin); 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; Given IV; Drug: cisplatin; Given IV

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ann Mauer, University of Chicago Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: February 10, 2004
• First Submitted That Met QC Criteria: February 11, 2004
• First Posted (Estimate): February 12, 2004

Study Record Updates

• Last Update Posted (Estimate): October 8, 2013
• Last Update Submitted That Met QC Criteria: October 7, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: NCI-2012-02576 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM62201 (U.S. NIH Grant/Contract); CDR0000352307; UCCRC-12765A; NCI-6285; 12765A (Other Identifier: University of Chicago Comprehensive Cancer Center); 6285 (Other Identifier: CTEP)