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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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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
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* Drug: Cefazolin
* Procedure: Resection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |