Arsenic Trioxide, Fluorouracil, and Leucovorin in Treating Patients With Stage IV Colorectal Cancer That Has Relapsed or Not Responded to Treatment

• Status: Completed
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Arsenic trioxide may help fluorouracil and leucovorin work better by making tumor cells more sensitive to the drugs. Giving arsenic trioxide together with fluorouracil and leucovorin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide and fluorouracil when given together with leucovorin in treating patients with stage IV colorectal cancer that has relapsed or not responded to treatment.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Miami
• Treatments: Arsenic Trioxide; Calcium; Fluorouracil; Leucovorin; Levoleucovorin

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer

• Stage IV disease (i.e., any T, any N, M1 disease)

• Relapsed or refractory disease

• Disease progressed after ≥ 2 different fluorouracil-containing chemotherapy regimens (e.g., irinotecan hydrochloride or oxaliplatin with or without bevacizumab)

• Bidimensionally measurable disease

• Must have tumor amenable to biopsy and be willing to undergo fine-needle aspiration

• No CNS metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy > 2 months

• Platelet count > 100,000/mm^3

• WBC ≥ 3,000/mm^3

• Creatinine ≤ 1.5 times upper limit of normal

• Bilirubin ≤ 2 times normal

• SGOT ≤ 5 times normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for at least 4 months after completion of study treatment

• No preexisting peripheral neuropathy ≥ grade 2

• Ejection fraction ≥ 30%

• Baseline QT interval < 500 msec

• No serious underlying medical illness or active infection

• No underlying medical condition that could be aggravated by the treatment

• No life-threatening disease unrelated to colorectal cancer

• No other malignancy within the past 5 years unless currently disease-free and all therapy for the malignancy has been completed

• No preexisting neurological disorder (i.e., seizure disorder) ≥ grade 3

• No cardiac disease, including any of the following:

• Recurrent supraventricular arrhythmia

• Any type of sustained ventricular arrhythmia or conduction block (e.g., grade II or III atrioventricular block or left bundle branch block)

• Uncontrolled ischemic heart disease

• History of nonsustained ventricular tachycardia

• Prolonged PR intervals (i.e., 1st degree heart block)

• No known hypersensitivity to arsenic trioxide or fluorouracil

• No history of allergic reactions attributed to compounds of similar biologic composition to arsenic trioxide or fluorouracil

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from all treatment-related toxicity

• At least 4 weeks since prior chemotherapy or radiotherapy and recovered

• More than 4 weeks since prior investigational drug

• No other concurrent investigational or commercial anticancer agent or therapy

• Concurrent local radiotherapy allowed for symptom relief (e.g., significant onset of pain after enrollment, but before beginning study therapy)