Comparative Study To Determine The Efficacy, Safety, And Tolerability Of Ceftolozane-Tazobactam

• Status: Active, not recruiting
• Trial end date: 2022-05-31
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this clinical research study is to learn if the study drug ceftolozane-tazobactam is more effective in controlling febrile neutropenia (fever and low white blood cell counts) than using approved antibiotics in patients with cancer. The safety of ceftolozane-tazobactam will also be studied.

This is an investigational study. Ceftolozane-tazobactam is FDA approved and commercially available to treat certain types of infections. It is not approved for the treatment of febrile neutropenia, either by itself or in combination with other antibiotics. Its use to treat febrile neutropenia is investigational.

All other antibiotics given on this study are FDA approved and commercially available for the treatment of infections. However, only cefepime is specifically FDA approved to treat febrile neutropenia. The study doctor can explain how the study drugs are designed to work.

Up to 100 participants will take part in this study. All will be enrolled at MD Anderson.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborators: Merck Sharp & Dohme Corp.; National Cancer Institute (NCI)
• Treatments: Cefepime; Ceftolozane; Ceftolozane, tazobactam drug combination; Cephalosporins; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam; Thienamycins

Criteria

Inclusion Criteria:

• Has provided written informed consent, and has the willingness and ability to comply with all study procedures

• Patients with neutropenic fever who have existing malignancy or have undergone hematopoietic stem cell transplantation; neutropenic fever is defined as the presence of neutropenia defined by: 1) absolute neutrophil count (ANC) < 500 cells/mm^3 or has an ANC that is expected to decrease to < 500 cells/mm^3 within 48 hours of trial entry and fever defined as: 2) single oral temperature measurement of > 101 degree Fahrenheit (F) (38.3 degree Celsius [C]) or a temperature of > 100.4 degree F (38.0 degree C) sustained over a 1-hour period

• Requires hospitalization for IV empiric antibiotic therapy

• If female: not breastfeeding; agrees to not attempt to become pregnant during the study; is surgically sterile or at least 2-years postmenopausal, or if of childbearing potential, has negative screening serum pregnancy test (if serum pregnancy test results are not available at the time of enrollment, a negative urine pregnancy test is required within 24 hours.); if of childbearing potential (including being < 2 years postmenopausal), is willing to practice sexual abstinence or use an effective dual form of contraception with her partner (eg, 2 barrier methods, barrier method plus hormonal method) during treatment and for ≥ 28 days after the last dose of any study therapy (IV or oral)

Exclusion Criteria:

• History of any hypersensitivity or allergic reaction to any cephalosporin antibiotic or tazobactam

• Fever suspected to be caused by a noninfectious cause (eg, fever related to drug or blood product administration)

• Confirmed fungal infection (eg, Pneumocystis jirovecii etiology in patients with pneumonia) that justifies adding additional empiric antimicrobial therapy (eg, antifungals)

• Confirmed viral infection that justifies adding additional empiric antiviral therapy (eg, ganciclovir, foscarnet)

• Known acute viral hepatitis

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 5 times the upper limit of normal (x ULN); patients with values > 3 x ULN and < 5 x ULN are eligible if the value is acute and directly related to the infectious process being treated

• Total bilirubin > 3 x ULN unless isolated hyperbilirubinemia is directly related to the acute infection or due to known Gilbert disease; manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy

• Known to be human immunodeficiency virus positive

• Severely impaired renal function, defined as creatinine clearance (CrCl) =< 30 mL/min estimated by the Cockcroft-Gault formula

• Expected requirement for hemodialysis while on study therapy

• Received > 24 hours of IV antibacterial therapy (with study drugs) within 72 hours of the initiation of inpatient IV study drug for treatment of suspected infection; antibiotic prophylaxis and oral antibiotics is allowed; prophylactic use of antiviral or antifungal medication is permitted

• Requirement for any non-study potentially effective concomitant systemic antibacterial therapy

• Past or current history of epilepsy or seizure disorder; exception: well-documented febrile seizure of childhood

• Evidence of immediately life-threatening disease, progressively fatal disease, or life expectancy of 3 months or less (eg, moribund or with shock unresponsive to fluid replacement)

• Unable or unwilling to adhere to the study-specified procedures and restrictions

• Any condition that would make the patient, in the opinion of the investigator, unsuitable for the study (eg, would place a patient at risk or compromise the quality of the data

• Participation in any other ongoing ceftolozane/tazobactam trial