Fever, Hot Flashes, Infection, Neutropenia, Sweating, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
neutropenia, infection, unspecified adult solid tumor, protocol specific, fever, sweats, and hot flashes
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.
Interventions
DRUGDaptomycin
daptomycin 6 mg/kg over 30 minutes every 24 hours until patient is afebrile and ANC is \>500 cells/mm\^3.
Sponsors
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Became Afebrile Within 72 Hours of Starting Daptomycin. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Daptomycin 6 mg/kg over 30 minutes every 24 hours until patient is afebrile and ANC is \>500 cells/mm\^3. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Daptomycin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 50.4 years STANDARD_DEVIATION 16.73 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
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.
Time frame: Within 72 hours of starting daptomycin
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daptomycin | Number of Participants Who Became Afebrile Within 72 Hours of Starting Daptomycin. | 16 participants |