The Impact of an Antibiotic (Cefazolin) Before Surgery on the Microbiome in Patients With Stage I-II Melanoma

Evaluating the Impact of Perioperative Antibiotic Prophylaxis on the Microbiome in Patients With Cutaneous Malignancy

This phase I trial investigates the impact of cefazolin before surgery on the microbiome in patients with stage I-II melanoma. Antibiotics, such as cefazolin, given at the time of surgery may cause a significant change in the microbes (like bacteria and viruses) found in the stomach and intestines. This trial may help researchers learn if any changes in microbes affect the body's ability to respond to surgery and cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Clinical Stage I Cutaneous Melanoma AJCC v8; Clinical Stage IA Cutaneous Melanoma AJCC v8; Clinical Stage IB Cutaneous Melanoma AJCC v8; Clinical Stage II Cutaneous Melanoma AJCC v8; Clinical Stage IIA Cutaneous Melanoma AJCC v8; Clinical Stage IIB Cutaneous Melanoma AJCC v8; Clinical Stage IIC Cutaneous Melanoma AJCC v8; Pathologic Stage I Cutaneous Melanoma AJCC v8; Pathologic Stage IA Cutaneous Melanoma AJCC v8; Pathologic Stage IB Cutaneous Melanoma AJCC v8; Pathologic Stage II Cutaneous Melanoma AJCC v8; Pathologic Stage IIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIC Cutaneous Melanoma AJCC v8
• Intervention / Treatment: Drug: Cefazolin; Procedure: Resection

Detailed Description

PRIMARY OBJECTIVE:

I. To investigate whether the use of pre-operative prophylactic antibiotics administered during surgical resection substantially alters the patient's gut microbiome.

SECONDARY OBJECTIVES:

I. To characterize the dynamics of the immune response to surgical intervention in the absence and presence of pre-operative prophylactic antibiotics, focusing on the immune profile of the peripheral blood leukocytes as well as the balance of circulating pro- and anti-inflammatory cytokines and metabolomic profiles.

II. To assess surgical site infection (SSI) in the absence and presence of pre-operative prophylactic antibiotics at time of surgical resection.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive cefazolin intravenously (IV) and then undergo standard of care surgical resection within 1 hour.

ARM B: Patients undergo standard of care surgical resection.

After completion of study treatment, patients are followed up at 3 days, 2 weeks, and 3 months.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Emily Z. Keung; Phone Number: 713-792-6940; Email: ekeung@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult subjects with early stage melanoma (stage I-II)
• Patients must be undergoing wide local excision +/- sentinel lymph node biopsy
• Patients must be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Exclusion Criteria:

• Use of antibiotics within the three months prior to surgery
• Allergy, sensitivity or anaphylaxis to beta-lactam or cephalosporin antibiotics
• Presence of an infection at the time of surgery
• Increased risk of infection due to a co-existing medical condition as determined by the surgical team or principal investigator (PI)
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration
• American Society of Anesthesiologists (ASA) grade > IV
• Refusal to participate in the study
• Patients who are pregnant will not be included in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (cefazolin, surgical resection); Patients receive cefazolin IV and then undergo standard of care surgical resection within 1 hour.	Drug: Cefazolin; Given IV; Procedure: Resection; Undergo standard of care surgical resection; Other Names: Surgical Resection
Experimental: Arm B (surgical resection); Patients undergo standard of care surgical resection.	Procedure: Resection; Undergo standard of care surgical resection; Other Names: Surgical Resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in microbiome alpha diversity	The diversity, structure, and composition of the fecal microbiome will be determined by 16S(v4) rRNA gene sequencing. 16S profiles will be used to compute alpha diversity, beta diversity, and the relative abundance of fecal bacteria. The composition of fecal bacteria in adult humans is mainly dominated by members of the Firmicutes and Proteobacteria phyla while members of Proteobacteria, Actinobacteria, Fusobacteria, and Verrucomicrobia are observed in lower abundance. To calculate richness (alpha-diversity), we will count each operational taxonomic unit (OTU) or amplicon sequence variant (ASV) identified. Richness count is expected to range between 10-500 per sample.	Baseline up to 2 weeks post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in relative abundance of microbes		Baseline, at 2 weeks post-surgery, and 3 months post-surgery
Change in microbiome diversity	The diversity, structure, and composition of the fecal microbiome will be determined by 16S(v4) rRNA gene sequencing. 16S profiles will be used to compute alpha diversity, beta diversity, and the relative abundance of fecal bacteria. The composition of fecal bacteria in adult humans is mainly dominated by members of the Firmicutes and Proteobacteria phyla while members of Proteobacteria, Actinobacteria, Fusobacteria, and Verrucomicrobia are observed in lower abundance. To calculate richness (alpha-diversity), we will count each operational taxonomic unit (OTU) or amplicon sequence variant (ASV) identified. Richness count is expected to range between 10-500 per sample.	Baseline up to 3 months post-surgery
Wound (surgical site) infection rate		Up to 3 months post-surgery
Profiling of systemic immune function by analysis of composition of circulating immune cell populations and cytokines	By analysis of composition of circulating immune cell populations and cytokines.	Up to 3 months post-surgery

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Emily Z Keung, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Estimated): February 2, 2027
• Study Completion (Estimated): February 2, 2027

Study Registration Dates

• First Submitted: October 5, 2020
• First Submitted That Met QC Criteria: May 3, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Skin Neoplasms; Anti-Infective Agents; Anti-Bacterial Agents; Cefazolin
• Other Study ID Numbers: 2020-0265 (Other Identifier: M D Anderson Cancer Center); NCI-2020-07071 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No