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

Phase 1

Active, not recruiting

Conditions: Clinical Stage I Cutaneous Melanoma AJCC v8
Clinical Stage IA Cutaneous Melanoma AJCC v8
Clinical Stage IIB Cutaneous Melanoma AJCC v8
Pathologic Stage IIB Cutaneous Melanoma AJCC v8
Pathologic Stage IIC Cutaneous Melanoma AJCC v8
Pathologic Stage I Cutaneous Melanoma AJCC v8
Pathologic Stage IB Cutaneous Melanoma AJCC v8
Pathologic Stage IIA Cutaneous Melanoma AJCC v8
Clinical Stage IB Cutaneous Melanoma AJCC v8
Clinical Stage II Cutaneous Melanoma AJCC v8

Brief Summary: 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.

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Arm A (cefazolin, surgical resection)	Resection	Patients receive cefazolin IV and then undergo standard of care surgical resection within 1 hour.
Arm A (cefazolin, surgical resection)	Cefazolin	Patients receive cefazolin IV and then undergo standard of care surgical resection within 1 hour.
Arm B (surgical resection)	Resection	Patients undergo standard of care surgical resection.

Primary Outcome Measures

Name	Time	Method
Change in microbiome alpha diversity	Baseline up to 2 weeks post-surgery	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.

Secondary Outcome Measures

Name	Time	Method
Change in microbiome diversity	Baseline up to 3 months post-surgery	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.
Profiling of systemic immune function by analysis of composition of circulating immune cell populations and cytokines	Up to 3 months post-surgery	By analysis of composition of circulating immune cell populations and cytokines.
Change in relative abundance of microbes	Baseline, at 2 weeks post-surgery, and 3 months post-surgery
Wound (surgical site) infection rate	Up to 3 months post-surgery