Moxifloxacin Compared With Ciprofloxacin/Amoxicillin in Treating Fever and Neutropenia in Patients With Cancer

Condition(s) targeted: Chronic Myeloproliferative Disorders; Fever, Sweats, and Hot Flashes; Infection; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Neutropenia; Unspecified Adult Solid Tumor, Protocol Specific

Intervention: amoxicillin-clavulanate potassium (Drug); ciprofloxacin (Drug); moxifloxacin hydrochloride (Drug); management of therapy complications (Procedure)

Phase: N/A

Status: Active, not recruiting

Sponsored by: European Organization for Research and Treatment of Cancer

Official(s) and/or principal investigator(s):
Winfried Kern, MD, Affiliation: University Hospital Freiburg

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.

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)

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

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

Secondary outcome:

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

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Cliniques Universitaires Saint-Luc, Brussels 1200, Belgium

Hopital Universitaire Erasme, Brussels 1070, Belgium

U.Z. Gasthuisberg, Leuven B-3000, Belgium

Institut Bergonie, Bordeaux 33076, France

Institut Curie Hopital, Paris 75248, France

Charite - Campus Charite Mitte, Berlin D-10117, Germany

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin, Berlin D-12200, Germany

Frauenklinik - Universitaetsklinikum Rostock am Klinikum Sudstadt, Rostock D-18057, Germany

Klinikum der Albert - Ludwigs - Universitaet Freiburg, Freiburg D-79106, Germany

Klinikum der Stadt Mannheim, Mannheim D-68135, Germany

Medizinische Universitaetsklinik I at the University of Cologne, Cologne D-50924, Germany

Ruprecht - Karls - Universitaet Heidelberg, Heidelberg D-69117, Germany

Universitaetsklinikum Ulm, Ulm D-89081, Germany

Wolfson Medical Center, Holon 58100, Israel

Istituto Nazionale per la Ricerca sul Cancro, Genoa 16132, Italy

Universita Degli Studi di Udine, Udine 33100, Italy

National Cancer Institute - Bratislava, Bratislava 833 10, Slovakia

St. Elizabeth Cancer Institute Hospital, Bratislava SK-81250, Slovakia

Centre Hospitalier Universitaire Vaudois, Lausanne CH-1011, Switzerland

Hopital D'Yverdon, Yverdon CH-1400, Switzerland

Hacettepe University - Faculty of Medicine, Ankara 06100, Turkey

Ibn-i Sina Hospital, Ankara 06100, Turkey

Marmara University Hospital, Istanbul 81190, Turkey

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

Starting date: April 2002
Last updated: May 23, 2008