Daptomycin in Treating Neutropenia and Fever in Patients With Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00335478
First received: June 8, 2006
Last updated: May 24, 2012
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Fever
Sweating
Hot Flashes
Infection
Neutropenia
Unspecified Adult Solid Tumor, Protocol Specific
Drug: Daptomycin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Phase II Open Label Pilot Trial of Empiric Daptomycin Treatment for Oncology Patients With Neutropenic Fever

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Number of Participants Who Became Afebrile Within 72 Hours of Starting Daptomycin. [ Time Frame: Within 72 hours of starting daptomycin ] [ Designated as safety issue: No ]

    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.



Enrollment: 54
Study Start Date: December 2006
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daptomycin Drug: Daptomycin
daptomycin 6 mg/kg over 30 minutes every 24 hours until patient is afebrile and ANC is >500 cells/mm^3.
Other Name: Cubicin

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00335478

Locations
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Principal Investigator: Joseph Bubalo, PharmD OHSU Knight Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00335478     History of Changes
Other Study ID Numbers: CDR0000476568, OHSU-CPC-05052-L, OHSU-1321, CUBIST-OHSU-CPC-05052-L
Study First Received: June 8, 2006
Results First Received: June 7, 2011
Last Updated: May 24, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by OHSU Knight Cancer Institute:
neutropenia
infection
unspecified adult solid tumor, protocol specific
fever, sweats, and hot flashes

Additional relevant MeSH terms:
Fever
Neutropenia
Hot Flashes
Body Temperature Changes
Signs and Symptoms
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Daptomycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014