Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Supportive care Closed any age EORTC-46852

Objectives

I.  Determine whether the combination of ceftazidime/amikacin/vancomycin is 
more efficacious than ceftazidime/amikacin as empiric therapy, particularly 
for gram positive organisms, in febrile granulocytopenic cancer patients.
II.  Compare the tolerance and toxicity of ceftazidime/amikacin/vancomycin 
with that of ceftazidime/amikacin.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Granulocytopenic (absolute 
granulocyte count of less than 1,000/microliter) adults and children with 
acute leukemia, marrow aplasia, or with solid tumors who have undergone bone 
marrow transplantation, and children under age 18 with these conditions or 
with a solid malignancy who have a fever above 38 degrees C (100.4 degrees F) 
and a presumed infection.  In institutions that are not also participating in 
EORTC trial VI (46853), patients with non-Hodgkin's lymphoma in whom 
chemotherapy-related profound granulocytopenia is expected to last more than 
10 days may be entered.  Patients randomized to intravenous aztreonam in trial 
Va (46851) who develop fever and granulocytopenia are also eligible.  A serum 
creatinine level no higher than 3.5 mg/dl (300 micromol/l) or an estimated 
creatinine clearance above 30 ml/minute are required.  Patients in renal 
failure and requiring hemo- or peritoneal dialysis are excluded, as are those 
who have a known allergy to any of the antibiotics used in this trial or a 
history of an immediate or accelerated reaction to penicillin or cephalosporin 
antibiotics; those with a high probability of death within 48 hours (e.g., 
moribund, comatose patients with little hope of neurological recovery or those 
in danger of or in a hepatic stupor or coma) are ineligible.  At least 4 days 
must have elapsed since patients received any antecedent therapeutic systemic 
antimicrobial agents, except for patients on trial Va (46851) as above and 
those who are receiving oral nonabsorbable antibiotics, oral antifungals, oral 
cotrimoxazole, or intravenous aztreonam infection prophylaxis.  Patients who 
are pregnant or lactating are not eligible.  Patients may be included in the 
study more than once if they have not received protocol or other intravenous 
antibiotic therapy for at least 4 days (96 hours) and if an interval of at 
least 7 days is allowed before re-entry on protocol.

Expected Enrollment

32 patients with single gram positive bacteraemia will be entered in each 
treatment arm; since only 10% of patients entered will have single gram 
positive bacteraemia, a total of 640 patients will be required.

Outline

Randomized study.
Arm I:  3-Drug Antibiotic Therapy.  Ceftazidime; Amikacin; Vancomycin.
Arm II:  2-Drug Antibiotic Therapy.  Ceftazidime; Amikacin.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Maurice J. Staquet, MD, Protocol chair		Ph: 32-2-541-3501