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

This study has been terminated.
(low accrual)
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00062231
First received: June 5, 2003
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention
Chronic Myeloproliferative Disorders
Fever, Sweats, and Hot Flashes
Infection
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Neutropenia
Precancerous Condition
Unspecified Adult Solid Tumor, Protocol Specific
Drug: amoxicillin-clavulanate potassium
Drug: ciprofloxacin
Drug: moxifloxacin hydrochloride
Procedure: management of therapy complications

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Supportive Care
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)

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Lymphoma, Small Cleaved-cell, Diffuse Multiple Myeloma Chronic Myeloproliferative Disorders Acute Lymphoblastic Leukemia Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Hodgkin Lymphoma Waldenstrom Macroglobulinemia Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic/myeloproliferative Disease Acute Myeloid Leukemia, Adult Follicular Lymphoma B-cell Lymphomas Myelofibrosis Burkitt Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoblastic Lymphoma Anaplastic Large Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Chronic Myelomonocytic Leukemia Chronic Neutrophilic Leukemia Hypereosinophilic Syndrome Monoclonal Gammopathy of Undetermined Significance Mantle Cell Lymphoma Cutaneous T-cell Lymphoma AL Amyloidosis Leukemia, T-cell, Chronic Essential Thrombocythemia Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Hairy Cell Leukemia Mycosis Fungoides Sezary Syndrome Large Granular Lymphocyte Leukemia Anaplastic Plasmacytoma Polycythemia Vera Granulocytopenia
U.S. FDA Resources

Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

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

Secondary Outcome 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

Enrollment: 351
Study Start Date: April 2002
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00062231

Locations
Belgium
Cliniques Universitaires Saint-Luc
Brussels, Belgium, 1200
Hopital Universitaire Erasme
Brussels, Belgium, 1070
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
France
Institut Bergonie
Bordeaux, France, 33076
Institut Curie Hopital
Paris, France, 75248
Germany
Charite - Campus Charite Mitte
Berlin, Germany, D-10117
Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
Berlin, Germany, D-12200
Medizinische Universitaetsklinik I at the University of Cologne
Cologne, Germany, D-50924
Klinikum der Albert - Ludwigs - Universitaet Freiburg
Freiburg, Germany, D-79106
Ruprecht - Karls - Universitaet Heidelberg
Heidelberg, Germany, D-69117
Klinikum der Stadt Mannheim
Mannheim, Germany, D-68135
Frauenklinik - Universitaetsklinikum Rostock am Klinikum Sudstadt
Rostock, Germany, D-18057
Universitaetsklinikum Ulm
Ulm, Germany, D-89081
Israel
Wolfson Medical Center
Holon, Israel, 58100
Italy
Istituto Nazionale per la Ricerca sul Cancro
Genoa, Italy, 16132
Universita Degli Studi di Udine
Udine, Italy, 33100
Slovakia
National Cancer Institute - Bratislava
Bratislava, Slovakia, 833 10
St. Elizabeth Cancer Institute Hospital
Bratislava, Slovakia, SK-81250
Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Hopital D'Yverdon
Yverdon, Switzerland, CH-1400
Turkey
Hacettepe University - Faculty of Medicine
Ankara, Turkey, 06100
Ibn-i Sina Hospital
Ankara, Turkey, 06100
Marmara University Hospital
Istanbul, Turkey, 81190
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Winfried Kern, MD University Hospital Freiburg
  More Information

Additional Information:
No publications provided by European Organisation for Research and Treatment of Cancer - EORTC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00062231     History of Changes
Other Study ID Numbers: EORTC-46001, EORTC-46001
Study First Received: June 5, 2003
Last Updated: September 20, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
infection
neutropenia
fever, sweats, and hot flashes
unspecified adult solid tumor, protocol specific
stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
monoclonal gammopathy of undetermined significance
recurrent adult Hodgkin lymphoma
stage I cutaneous T-cell non-Hodgkin lymphoma
stage II cutaneous T-cell non-Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
isolated plasmacytoma of bone
extramedullary plasmacytoma
refractory multiple myeloma
stage 0 chronic lymphocytic leukemia
Waldenstrom macroglobulinemia
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia

Additional relevant MeSH terms:
Neoplasms
Fever
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Neutropenia
Precancerous Conditions
Lymphoma, Large-Cell, Immunoblastic
Hot Flashes
Myelodysplastic-Myeloproliferative Diseases
Body Temperature Changes
Signs and Symptoms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on April 17, 2014