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

Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00062231
• Other study ID #: EORTC-46001
• Secondary ID: EORTC-46001
• Status: Terminated
• Phase: N/A
• First received: June 5, 2003
• Last updated: September 20, 2012
• Start date: April 2002

Study information

• Verified date: September 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 351
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Fever
• Fever, Sweats, and Hot Flashes
• Hot Flashes
• Infection
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Neoplasms
• Neoplasms, Plasma Cell
• Neutropenia
• Plasmacytoma
• Precancerous Condition
• Precancerous Conditions
• Preleukemia
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• amoxicillin-clavulanate potassium

• ciprofloxacin

• moxifloxacin hydrochloride

Procedure:
• management of therapy complications

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	U.Z. Gasthuisberg	Leuven
France	Institut Bergonie	Bordeaux
France	Institut Curie Hopital	Paris
Germany	Charite - Campus Charite Mitte	Berlin
Germany	Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Medizinische Universitaetsklinik I at the University of Cologne	Cologne
Germany	Klinikum der Albert - Ludwigs - Universitaet Freiburg	Freiburg
Germany	Ruprecht - Karls - Universitaet Heidelberg	Heidelberg
Germany	Klinikum der Stadt Mannheim	Mannheim
Germany	Frauenklinik - Universitaetsklinikum Rostock am Klinikum Sudstadt	Rostock
Germany	Universitaetsklinikum Ulm	Ulm
Israel	Wolfson Medical Center	Holon
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genoa
Italy	Universita Degli Studi di Udine	Udine
Slovakia	National Cancer Institute - Bratislava	Bratislava
Slovakia	St. Elizabeth Cancer Institute Hospital	Bratislava
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Hopital D'Yverdon	Yverdon
Turkey	Hacettepe University - Faculty of Medicine	Ankara
Turkey	Ibn-i Sina Hospital	Ankara
Turkey	Marmara University Hospital	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Israel,  Italy,  Slovakia,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response as measured by International Antimicrobial Therapy Group (IATG) specific criteria at the completion of allocated treatment
Secondary	Rate of complication as measured by Multinational Association for Supportive Care in Cancer (MASCC) criteria at the end of febrile neutropenic episode
Secondary	Time to discharge as measured by Logrank continuously until the end of febrile neutropenic episode
Secondary	Time to defervescence as measured by Logrank continuously until the end of febrile neutropenic episode
Secondary	Survival status as measured by Logrank at day 28