Daptomycin in Treating Neutropenia and Fever in Patients With Cancer

Phase II Open Label Pilot Trial of Empiric Daptomycin Treatment for Oncology Patients With Neutropenic Fever

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.

Study Overview

• Status: Completed
• Conditions: Hot Flashes; Neutropenia; Fever; Unspecified Adult Solid Tumor, Protocol Specific; Infection; Sweating
• Intervention / Treatment: Drug: Daptomycin

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Cubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Became Afebrile Within 72 Hours of Starting Daptomycin.	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.	Within 72 hours of starting daptomycin

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Investigators: Principal Investigator: Joseph Bubalo, PharmD, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: June 8, 2006
• First Submitted That Met QC Criteria: June 8, 2006
• First Posted (Estimate): June 12, 2006

Study Record Updates

• Last Update Posted (Actual): May 9, 2017
• Last Update Submitted That Met QC Criteria: May 7, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific; infection; neutropenia; fever, sweats, and hot flashes
• Additional Relevant MeSH Terms: Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Body Temperature Changes; Neutropenia; Fever; Hot Flashes; Anti-Infective Agents; Anti-Bacterial Agents; Daptomycin
• Other Study ID Numbers: CDR0000476568; OHSU-CPC-05052-L (Other Identifier: OHSU Knight Cancer Institute); OHSU-1321 (Other Identifier: OHSU IRB); CUBIST-OHSU-CPC-05052-L (Other Identifier: Cubist Pharmaceuticals)