Daptomycin in Treating Neutropenia and Fever in Patients With Cancer

OHSU Knight Cancer Institute

Status and phase

Completed

Phase 2

Conditions

Fever

Infection

Unspecified Adult Solid Tumor, Protocol Specific

Neutropenia

Hot Flashes

Sweating

Treatments

Drug: Daptomycin

Study type

Interventional

Funder types

Other

Identifiers

NCT00335478

CDR0000476568

OHSU-1321 (Other Identifier)

OHSU-CPC-05052-L (Other Identifier)

CUBIST-OHSU-CPC-05052-L (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

54 patients

Sex

All

Ages

18 to 99 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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