Official Title: “A Prospective Randomised Phase III Trial of Early Hospital Discharge Versus Standard Inpatient Management of Cancer Patients With Low-Risk Febrile Neutropenia Receiving Oral Antibiotics. Oral Antibiotics for Neutropenic Sepsis Giving Early Hospital Discharge [ORANGE]”

RATIONALE: Finishing an antibiotic regimen at home may be as effective as receiving it in the hospital. It is not yet known whether early hospital discharge is as effective as standard inpatient care in cancer patients receiving antibiotics for febrile neutropenia.

PURPOSE: This randomized phase III trial is studying early hospital discharge and comparing it with standard inpatient care in cancer patients receiving antibiotics for febrile neutropenia.

Study Type: Interventional

Study Design: Supportive Care, Randomized

Study Primary Completion Date: July 2010

OBJECTIVES: - Identify cancer patients who are low-risk inpatients and meet criteria for early discharge (i.e., symptomatic improvement and temperature ≤ 37.8°C) after receiving oral antibiotics for febrile neutropenia.

OUTLINE: This is a randomized, prospective, multicenter study. Patients are stratified by disease type (lymphoma vs solid tumor), duration of registration (< 48 hours vs > 48 hours), and participating center.

Patients receive oral amoxicillin-clavulanate potassium 3 times daily and oral ciprofloxacin twice daily on admission to the hospital. Treatment continues for 7 days in the absence of clinical deterioration or unacceptable toxicity. Patients are assessed as inpatients after ≥ 24 and up to 72 hours after the first antibiotic dose. Patients showing clear response (i.e., symptomatic improvement irrespective of neutrophil recovery, temperature ≤ 37.8 C for 24 hours) and who continue to meet study eligibility criteria are randomized to 1 of 2 arms. - Arm I (early discharge): Patients are discharged home and instructed to remain in daily contact with hospital staff to report temperature and symptoms until completion of oral antibiotic regimen. - Arm II (standard management): Patients continue their antibiotic course in hospital and are discharged according to local guidelines and the following additional criteria:

subjective improvement, afebrile (≤ 37°C for 24 hours), and absolute neutrophil count ≥ 500/mm³ and rising.

Patients in both arms complete a daily diary documenting daily temperature readings, symptoms, and toxicities. Patients also complete a Health Questionnaire and a Cancer Worries Inventory Booklet at baseline, in the hospital immediately after randomization, and at completion of oral antibiotics or resolution of neutropenic febrile episode.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: amoxicillin-clavulanate potassium
• Drug: ciprofloxacin
• Procedure: psychosocial assessment and care
• Procedure: quality-of-life assessment

Primary Measures

• Total number of days of hospitalization (including unplanned readmission) (randomized patients)
• Incidence of serious adverse events (randomized and registered patients)

Secondary Measures

• Incidence of treatment failure as defined by the necessity for change in antibiotic therapy (randomized and registered patients)
• Incidence of unplanned readmissions (randomized patients)
• Patient acceptability of randomized discharge policy as measured by Health Questionnaire, Cancer Worries Inventory Booklet, and Patient Daily Diary (randomized patients)
• Toxicity attributed to oral antibiotic therapy as measured by NCI CTCAE v3.0 (randomized and registered patients)
• Health service costs (randomized patients)

DISEASE CHARACTERISTICS:

• Diagnosis of solid tumor or lymphoma AND meets the following criteria:
• Low-risk patient, defined as Multinational Association for Supportive Care in Cancer prognostic index score ≥ 21
• Presents with neutropenic fever defined as follows:
• Absolute neutrophil count ≤ 500/mm³ OR < 1,000/mm³ but anticipated to fall to ≤ 500/mm³ within 24 hours of study entry
• Temperature ≥ 38.5°C on a single measurement or ≥ 38.0°C on > 1 occasion (one of which could be measured by the patient prior to admission) ≥ 1 hour apart
• Undergoing concurrent cytotoxic chemotherapy for treatment of solid tumors or lymphoma
• No leukemia

PATIENT CHARACTERISTICS:

• Compliant and appropriate for early discharge
• Able to read a thermometer (patient or caregiver)
• Able to tolerate oral medication
• Must have a responsible adult caregiver if eligible for early discharge
• No known allergy to oral antibiotics or penicillin
• No requirement for IV fluid support
• No central venous catheter-associated infection or evidence of infection not amenable to treatment by study antibiotics
• No neutropenic fever at high risk of complications
• No associated comorbidity that requires hospitalization and management
• No known HIV positivity

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior participation in this study for neutropenic episode
• No prior bone marrow transplantation or peripheral blood stem cell transplantation
• No prior treatment for leukemia
• More than 72 hours since prior antibiotics, including prophylactic antibiotics
• Prophylactic septrin (for pneumocystis), acyclovir, or antifungals are allowed
• No concurrent granulocyte colony-stimulating factor therapy

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: Clatterbridge Centre for Oncology

Overall Clinical Trial Officials and Contacts

Ernest Marshall, MD Study Chair Clatterbridge Centre for Oncology  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00445497

Study ID Number: CDR0000533828

ClinicalTrials.gov Identifier: NCT00445497

Health Authority: Unspecified

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