Phase II Open Label Pilot Trial of Empiric Daptomycin Treatment for Oncology Patients With Neutropenic Fever
18 Years
N/A
Both
Fever, Sweating, Hot Flashes, Infection, Neutropenia, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Phase II Open Label Pilot Trial of Empiric Daptomycin Treatment for Oncology Patients With Neutropenic Fever
OBJECTIVES:
Primary
- Assess the response rate to therapy within 72 hours of starting daptomycin in cancer
patients with neutropenic fever.
Secondary
- Assess the percentage of bacterial cures in patients with documented gram-positive
bacterial infections.
- Assess time to afebrile state.
- Assess the pharmacokinetic data of daptomycin in neutropenic patients.
- Document the incidence of breakthrough infections that require a change of therapy or
additional agents to clear.
- Assess the tolerability of daptomycin in neutropenic patients.
- Assess and document adverse events and toxicity due to daptomycin.
OUTLINE: This is an open-label, pilot study.
Patients first receive standard treatment for gram-negative bacteria for 72 hours. If the
patient is still febrile at 72 hours, daptomycin is administered.
Patients receive daptomycin IV over 30 minutes once daily. Patients who are afebrile, not
neutropenic (absolute neutrophil count [ANC] > 500/mm³), and have no signs of infection
after 72 hours of therapy may discontinue daptomycin. Patients who are afebrile and
neutropenic (ANC < 500/mm³) after 72 hours of therapy continue to receive daptomycin until
absolute neutrophil count (ANC) > 500/mm³ for 2 consecutive days. Patients who are febrile
with or without continued neutropenia (ANC < 500/mm³) after 72 hours of therapy continue to
receive daptomycin for up to 10-14 days in the absence of unacceptable toxicity.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of cancer
- Diagnosis of neutropenic fever
- Temperature > 38.3°C once OR ≥ 38°C twice within 12 hours
- Absolute neutrophil count < 500/mm^³ and ≥ 1 of the following:
- Mucositis
- Concurrent skin or soft tissue infection
- Indwelling catheter and/or suspected catheter infection
- Recent quinolone prophylaxis
- Positive blood cultures for gram-positive cocci before final identification
or other documented gram-positive pathogen
- Colonization with β-lactam resistant gram-positive organisms (commonly the
nares or the skin)
- Hypotension, tachycardia, narrowed pulse pressures, tachypnea, or other
signs of cardiovascular compromise
- Expected duration of neutropenia ≥ 3 days
- No known infection with daptomycin-resistant organism or gram-negative organism and
not yet meeting criteria for the addition of gram-positive antimicrobial therapy
- No suspected meningitis or osteomyelitis
- No documented or suspected gram-positive pneumonia
- No suspected or proven endocarditis
PATIENT CHARACTERISTICS:
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Life expectancy ≥ 2 weeks
- Creatinine clearance ≥ 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-method contraception
- No known sensitivity to daptomycin or product excipients
- No history of or concurrent rhabdomyolysis
- No HIV positivity
- No psychiatric disorders that would preclude study compliance
- No signs or symptoms of myopathy with creatine phosphokinase (CPK) elevation > 1,000
U/L (5 times upper limit of normal [ULN])
- No CPK elevations > 10 times ULN in patients with no signs or symptoms of
myopathy
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 7 days since prior daptomycin or other antibiotic agents covering
gram-positive organisms
- No concurrent hemodialysis or continuous ambulatory peritoneal dialysis
- No concurrent succinylcholine, ethanol, fludrocortisone, olanzapine, or pioglitazone
- No concurrent hydroxymethyl glutaryl (HMG) coenzyme A (HMG CoA) reductase inhibitors
(e.g., lovastatin, simvastatin, atorvastatin)
- Concurrent therapy for gram-negative bacterial infection allowed
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
Number of Participants Who Became Afebrile Within 72 Hours of Starting Daptomycin.
Outcome Description:
If after 72 hours of daptomycin treatment, the patient is afebrile and has absolute neutrophil count (ANC) >500 cells/mm^3 for 48 hours with no site of infection, negative cultures, and no clinical indications for therapy, the antibiotic regimen will be discontinued. Complete Response: Resolution of fever and clinical signs/symptoms of infection. Partial Response: Resolution of fever without resolution of clinical signs of infection.
Outcome Time Frame:
Within 72 hours of starting daptomycin
Safety Issue:
No
Principal Investigator
Joseph Bubalo, PharmD
Investigator Role:
Principal Investigator
Investigator Affiliation:
OHSU Knight Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000476568
NCT ID:
NCT00335478
Start Date:
December 2006
Completion Date:
October 2008
Related Keywords:
- Fever
- Sweating
- Hot Flashes
- Infection
- Neutropenia
- Unspecified Adult Solid Tumor, Protocol Specific
- neutropenia
- infection
- unspecified adult solid tumor, protocol specific
- fever, sweats, and hot flashes
- Fever
- Neutropenia
- Hot Flashes
Name | Location |
|---|---|
| OHSU Knight Cancer Institute | Portland, Oregon 97239 |
