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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Supportive care	Completed	any age	NCI	NCI-85-C-212C NCI-T86-0036N, T86-0036

Objectives

I.  Compare the relative benefits and disadvantages of two novel beta-lactam 
antibiotics (ceftazidime vs. Primaxin) in the initial management of 
febrile-granulocytopenic cancer patients.
II.  Determine whether oral antimicrobial therapy is as effective as 
parenteral therapy after the initial 72 hours of empiric antibiotics.
III.  Determine whether there is a safer and more effective alternative to 
amphotericin-B as antifungal therapy for patients who remain febrile in spite 
of antibiotic therapy.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Cancer patients more than 4 years of 
age who are undergoing treatment in the Pediatric, Medicine, or Radiation 
Oncology Branches of the Clinical Oncology Program.  Patients younger than 4 
years may be treated nonrandomly on Arm I.  Patients must have fever and 
granulocytopenia, defined respectively as follows:  either 3 oral (or 
equivalent) temperatures above 38 degrees C (each at least 4 hours apart) 
during a single 24-hour period or a single oral (or equivalent) temperature 
elevation above 38.5 degrees C; and less than 500 polymorphonuclear leukocytes 
or bandforms/cumm.  Patients with an absolute granulocyte count between 500 
and 1,000/cumm that is rapidly falling following antecedent chemotherapy are 
also eligible; those with a documented or defined site of infection who are 
febrile and granulocytopenic are eligible as long as they have not received 
antibiotic therapy within the previous 72 hours (prophylactic 
trimethoprim/sulfamethoxazole is allowed) and they do not have a microbial 
isolate resistant to either ceftazidime or Primaxin.  Patients who appear 
clinically septic or infected, but who do not meet the criteria for fever and 
granulocytopenia, should be discussed with the NCI-ID fellow or the principal 
investigator regarding drug management.  Patients with no defined time to bone 
marrow recovery (i.e., with aplastic anemia) or with AIDS are excluded from 
randomization, as are those who are pregnant or nursing.  Patients with 
isolates or infections in whom resistance or failure is considered likely may 
not be randomized (i.e., those with meningitis or brain abscess; those with 
clostridial infection; and those with non-aeruginosa pseudomonal infections, 
e.g., P. maltophilia or P. capacia, or known infection with enterococcus, 
coagulase-negative staphylococci, or listeria).  Primary organ failure 
(hepatic or renal) excludes patients from randomization.  Patients with known 
allergy to beta-lactam antibiotics (i.e., Type I or anaphylactic reaction to 
penicillin) may not be randomized and should be discussed individually with 
the principal investigator; those whose only prior allergic reaction is a 
rash, particularly if non-urticarial, may be randomized (such patients should 
be discussed with the NCI-ID fellow on-call).

Expected Enrollment

125 evaluable patients with unexplained fever and 85 evaluable patients with 
documented infection will be required in each arm of the Initial Empiric 
Therapy Trial.  In the Route of Administration Trial, 90 evaluable patients 
with documented infection and 65 evaluable patients with unexplained fever 
will be required in each arm.

Outline

Patients are first randomized on the Initial Empiric Therapy Trial, with 
subsequent randomizations dependent on whether or not a source of defined 
infection is determined and on their response to Initial Empiric Therapy.
Initial Empiric Therapy Trial.
Arm I:  Single-agent Antibiotic Therapy.  Ceftazidime, CTZ.
Arm II:  Single-agent Antibiotic Therapy.  Primaxin (Imipenem plus 
Cilastatin). Salvage Regimen:  Antibiotic, Antiparasitic, and/or Antiviral 
Therapy as indicated.  One or more of the following agents or combination may 
be administered:  VGP:  Vancomycin; Gentamicin; Piperacillin; or Clindamycin; 
Metronidazole; Amphotericin-B; Ketoconazole; Acyclovir; or 
Trimethoprim-sulfamethoxazole.
Route of Administration Trial.
Arm I:  Single-agent Oral Antibiotic Therapy.  Ciprofloxacin or Augmentin 
(Amoxicillin plus Clavulanic acid).
Arm II:  Single-agent Parenteral Antibiotic Therapy.  CTZ or Primaxin.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Philip Pizzo, MD, Protocol chair		Ph: 650-724-5688 Email: philip.pizzo@stanford.edu