Arsenic Trioxide in Treating Patients With Pancreatic Cancer That Has Not Responded to Gemcitabine

A Phase II Study Of Arsenic Trioxide In Patients With Adenocarcinoma Of The Pancreas Refractory To Gemcitabine

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of arsenic trioxide in treating patients who have locally advanced or metastatic pancreatic cancer that has not responded to gemcitabine.

OBJECTIVES:

• Determine the objective response rate to arsenic trioxide in patients with pancreatic cancer who have progressed after first-line treatment with a gemcitabine-containing regimen when treated with arsenic trioxide.
• Determine the toxicity of this drug in these patients.
• Determine the duration of response, median and overall survival, and time to progression in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive arsenic trioxide IV over 1 hour on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 9-12 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

  • Locally advanced or metastatic disease

• Unidimensionally measurable disease

  • At least 1 lesion that is at least 20 mm with conventional techniques or at least 10 mm with spiral CT scan

• Must have progressed after chemotherapy with a gemcitabine-containing regimen

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 5 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• QTc less than 500 msec at baseline by EKG
• No New York Heart Association class III or IV heart failure
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to arsenic trioxide
• No other active malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy
• No concurrent colony-stimulating factors during the first course of the study

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior arsenic trioxide
• No other concurrent chemotherapy
• No more than 1 prior chemotherapy regimen for metastatic disease

Endocrine therapy

• No concurrent hormonal therapy

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent therapeutic radiotherapy

Surgery

• At least 4 weeks since major surgery

Other

• No other concurrent investigational or commercial anticancer agents or therapies
• No other concurrent investigational agents
• No concurrent antiretroviral therapy in HIV-positive patients
• No concurrent medications for other comorbid conditions that are known to prolong the QT interval