Clinical trial NCT00335478: Daptomycin in Treating Neutropenia and Fever in Patients With Cancer
Official title: Phase II Open Label Pilot Trial of Empiric Daptomycin Treatment for Oncology Patients With Neutropenic Fever
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fever
Sweating
Hot Flashes
Infection
Neutropenia
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: neutropenia
infection
unspecified adult solid tumor, protocol specific
fever, sweats, and hot flashes
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
First posted: 2006-06-12
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Antibiotics, such as daptomycin, may control neutropenia, fever, and infection in patients with cancer.

PURPOSE: This phase II trial is studying how well daptomycin works in treating neutropenia and fever in patients with cancer.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Number of Participants Who Became Afebrile Within 72 Hours of Starting Daptomycin.
timeFrame: Within 72 hours of starting daptomycin
Secondary outcomes:
Other outcomes:
Locations:
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Joseph Bubalo, PharmD
role: PRINCIPAL_INVESTIGATOR
References: