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

NCT03485950 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2017-0729NCI-2018-00755
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Other Infectious Diseases

Keywords

Other infectious diseases; Febrile neutropenic adults with cancer; Ceftolozane-Tazobactam; Cefepime; Meropenem; Piperacillin/Tazobactam

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Favorable Clinical Response at End of Inpatient Intravenous Therapy (EOIV)

  Resolution of all acute signs and symptoms of the primary infection or improvement to such an extent that no additional antibacterial therapy is required (ie, except for protocol-allowed adjunctive therapies and/or oral or IV switch) and such that no more than 14 days of total antibacterial therapy is required.

  Within 72 hours after administration of the last dose of inpatient IV study drug

Secondary Outcomes (23)

• Number of Participants With Favorable Clinical Response in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set at EOIV.

  Within 72 hours after administration of the last dose of inpatient IV study drug.

• Number of Participants With Favorable Clinical Response in the Clinically Evaluable (CE) Analysis Set at EOIV.

  Within 72 hours after administration of the last dose of inpatient IV study drug.

• Number of Participants With Favorable Clinical Response in the MITT Analysis Set at TOC

  21 to 28 days after the start of inpatient IV study drug

• Number of Participants With Favorable Clinical Response in the MITT Analysis Set at Late Follow-Up (LFU)

  35 to 42 days after the start of inpatient IV study drug

• Number of Participants With Favorable Clinical Response in the mMITT Analysis Set at Test of Cure (TOC)

  21 to 28 days after the start of inpatient IV study drug.

Study Arms (2)

Group I (ceftolozane-tazobactam)

EXPERIMENTAL

Participants receive ceftolozane-tazobactam IV over 1 hour every 8 hours for up to 14 days in the absence of disease progression or unacceptable toxicity. After at least 3 days, participants may switch to different PO or IV antibiotics at the discretion of the study doctor.

Drug: Ceftolozane; Other: Laboratory Biomarker Analysis; Drug: Tazobactam

Group II (standard of care antibiotic treatment)

ACTIVE COMPARATOR

Participants receive standard of care antibiotic treatment consisting of either cefepime IV over 30 minutes every 8 hours, meropenem IV over 30 minutes every 8 hours, or piperacillin-tazobactam IV over 1 hour every 6 hours for up to 14 days in the absence of disease progression or unacceptable toxicity.

Drug: Cefepime; Other: Laboratory Biomarker Analysis; Drug: Meropenem; Drug: Piperacillin-Tazobactam; Drug: Tazobactam

Interventions

Cefepime DRUG

Given IV

Group II (standard of care antibiotic treatment)

Ceftolozane DRUG

Given IV

Also known as: CXA-101

Group I (ceftolozane-tazobactam)

Laboratory Biomarker Analysis OTHER

Correlative studies

Group I (ceftolozane-tazobactam); Group II (standard of care antibiotic treatment)

Meropenem DRUG

Given IV

Also known as: Meropenem Trihydrate, Merrem I.V., SM-7338

Group II (standard of care antibiotic treatment)

Piperacillin-Tazobactam DRUG

Given IV

Also known as: PIPER/TAZO, Piperacillin/Tazobactam, Zosyn

Group II (standard of care antibiotic treatment)

Tazobactam DRUG

Given IV

Also known as: YTR-830H

Group I (ceftolozane-tazobactam); Group II (standard of care antibiotic treatment)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Chaftari AM, Hachem R, Malek AE, Mulanovich VE, Szvalb AD, Jiang Y, Yuan Y, Ali S, Deeba R, Chaftari P, Raad I. A Prospective Randomized Study Comparing Ceftolozane/Tazobactam to Standard of Care in the Management of Neutropenia and Fever in Patients With Hematological Malignancies. Open Forum Infect Dis. 2022 Feb 14;9(6):ofac079. doi: 10.1093/ofid/ofac079. eCollection 2022 Jun.

  PMID: 35663286 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Interventions

Cefepime; ceftolozane; Meropenem; Piperacillin, Tazobactam Drug Combination; Tazobactam

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thienamycins; Carbapenems; Penicillanic Acid; Penicillins; Piperacillin; Ampicillin; Penicillin G; Sulfones; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Issam Raad,MD - Chair, Infectious Diseases
• Organization: UT MD Anderson Cancer Center

iraad@mdanderson.org

(713) 792-7943

Study Officials

• Issam I Raad

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2018
• First Posted: April 3, 2018
• Study Start: May 16, 2018
• Primary Completion: May 1, 2021
• Study Completion: February 16, 2022
• Last Updated: March 15, 2022
• Results First Posted: July 20, 2021

Record last verified: 2022-03

Locations

US (1)