Official Title: “Oral Empirical Therapy of Fever in Low-Risk Neutropenic Cancer Patients: A Prospective, Double-Blind, Randomized, Multicenter Trial Comparing Monotherapy (Single Daily Dose Moxifloxacin) With Combination Therapy (Ciprofloxacin Plus Amoxicillin/Clavulanic Acid)”

RATIONALE: Antibiotics such as amoxicillin, ciprofloxacin, and moxifloxacin may be effective in preventing or controlling fever and neutropenia in patients with cancer. It is not yet known whether moxifloxacin alone is more effective than amoxicillin combined with ciprofloxacin in treating neutropenia and fever.

PURPOSE: This randomized clinical trial is studying how well moxifloxacin works and compares it to ciprofloxacin together with amoxicillin in treating neutropenia and fever in patients with cancer.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Active Control

OBJECTIVES: - Compare the rates of successful response to moxifloxacin vs ciprofloxacin in combination with amoxicillin-clavulanate potassium in low-risk febrile neutropenic patients with cancer. - Compare the time to discharge, time to discontinuation of any antimicrobial therapy, and time to defervescence of patients treated with these regimens. - Compare 28-day survival of patients treated with these regimens. - Determine the proportion of these patients who are eligible for oral therapy and a therapeutic management including intention of early discharge. - Determine the medical and nonmedical reasons for continued in-hospital observation and care or for readmission of these patients. - Determine the accuracy of the physician's estimate of further neutropenia duration and evaluate its predictive value in these patients. - Validate the Multinational Association for Supportive Care in Cancer low-risk prediction rule to predict the absence of serious medical complications in the setting of oral therapy in in- and outpatients.

OUTLINE: This is a double-blind, randomized, multicenter study. Patients are stratified according to institution, underlying disease (hematologic malignancy vs other), pretreatment with no more than a single dose (yes vs no), and outpatient status at fever onset (yes vs no). Patients are randomized into 1 of 2 treatment arms. - Arm I: Patients receive oral moxifloxacin once daily. Patients also receive oral ciprofloxacin placebo and oral amoxicillin-clavulanate potassium placebo twice daily. - Arm II: Patients receive oral ciprofloxacin and oral amoxicillin-clavulanate potassium twice daily. Patients also receive oral moxifloxacin placebo once daily.

Patients with fever classified as not related to infection (i.e., doubtful) stop antibiotic therapy on day 3. All other patients receive antibiotics until complete resolution of infection, or until failure is determined or anticipated, for up to 28 days.

Patients are followed at 7-10 days.

PROJECTED ACCRUAL: A total of 530 patients (265 patients per treatment arm) will be accrued for this study within approximately 2 years.

Intervention(s) in this Clinical Trial

• Drug: amoxicillin-clavulanate potassium
• Drug: ciprofloxacin
• Drug: moxifloxacin hydrochloride
• Procedure: management of therapy complications

Primary Measures

• Response as measured by International Antimicrobial Therapy Group (IATG) specific criteria at the completion of allocated treatment

Secondary Measures

• Rate of complication as measured by Multinational Association for Supportive Care in Cancer (MASCC) criteria at the end of febrile neutropenic episode
• Time to discharge as measured by Logrank continuously until the end of febrile neutropenic episode
• Time to defervescence as measured by Logrank continuously until the end of febrile neutropenic episode
• Survival status as measured by Logrank at day 28

DISEASE CHARACTERISTICS:

• Diagnosis of cancer with developing febrile neutropenia
• Neutropenia defined as an absolute granulocyte count of less than 1,000/mm^3, expected to fall to less than 500/mm^3 within 24 hours, secondary to administration of chemotherapy and/or radiotherapy within the past 30 days
• Fever defined as an oral temperature greater than 38.5ºC once, or 38°C or greater on 2 or more occasions at least 1 hour apart during a 12-hour period, and suspected to be due to infection
• Expected low risk of serious medical complications as predicted by a Multinational
• Association for Supportive Care in Cancer risk-index score of greater than 20
• No obvious signs of exit-site or tunnel intravascular catheter infection
• No known or suspected CNS infection
• No known or highly suspected bacterial, viral, or fungal infection

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• Not specified
• Life expectancy
• No high probability of death within 48 hours before study enrollment (i.e., patients who are moribund or comatose for any reason with little hope of recovery OR patients in danger of, or in hepatic stupor or coma)
• Hematopoietic
• See Disease Characteristics
• No signs or symptoms of uncontrolled bleeding
• Hepatic
• Bilirubin no greater than 3 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 3 times ULN
• AST and ALT no greater than 5 times ULN
• No severe hepatic dysfunction
• Renal
• Creatinine no greater than 3.4 mg/dL
• Creatinine clearance at least 25 mL/min
• No renal failure requiring hemodialysis or peritoneal dialysis
• Cardiovascular
• No prior symptomatic arrhythmias
• No clinically relevant bradycardia
• No QTc interval prolongation
• No uncorrected hypokalemia
• No signs or symptoms of hypotension (systolic less than 90 mm Hg)
• Pulmonary
• No signs or symptoms of respiratory insufficiency
• Other
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Able to swallow oral medication
• No contraindication for oral drug intake
• No condition likely to severely impair drug absorption
• No prior immediate or accelerated reaction to penicillin, cephalosporin, or fluoroquinolone antibiotics
• No known allergy or hypersensitivity to any antibiotics in this study or other quinolones
• No signs or symptoms of severe dehydration
• No signs or symptoms of shock
• No other signs or symptoms at presentation that would necessitate IV supportive therapy

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• Not specified
• Chemotherapy
• See Disease Characteristics
• Endocrine therapy
• Not specified
• Radiotherapy
• See Disease Characteristics
• Surgery
• Not specified
• Other
• More than 4 days since prior antibacterial agents except for the following:
• A single (oral or parenteral therapeutic) dose after initial diagnosic work-up and within the last 8 hours
• Low-dose cotrimoxazole (i.e., no more than 480 mg daily or 960 mg 3 times per week) prophylaxis of Pneumocystis carinii pneumonia
• More than 30 days since prior investigational drugs
• No prior randomization in this study
• No other concurrent antimicrobial agents
• No class IA or class III antiarrhythmic drugs or other concurrent drugs that prolong the QTc interval

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: European Organization for Research and Treatment of Cancer

Overall Clinical Trial Officials and Contacts

Winfried Kern, MD  University Hospital Freiburg  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00062231

Study ID Number: CDR0000304631

ClinicalTrials.gov Identifier: NCT00062231

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database