Antibiotics Before Surgery for Melanoma

Overseen By Emily Z. Keung

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antibiotics, Corticosteroids, Immunosuppressives

Disqualifiers: Infection, Pregnancy, ASA grade > IV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the antibiotic cefazolin affects the gut microbiome—the community of bacteria and viruses in the stomach and intestines—in individuals with early-stage melanoma undergoing surgery. Researchers aim to determine if cefazolin taken before surgery alters these microbes and impacts the body's response to surgery and cancer. Participants will either receive cefazolin before their surgical procedure or undergo surgery without it. The trial seeks adults with stage I-II melanoma scheduled for surgery involving a wide local excision (also known as resection), with or without a biopsy of nearby lymph nodes. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have used antibiotics in the three months before surgery or be on certain immune system medications within 14 days of the study drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cefazolin, an antibiotic, is usually well-tolerated when administered before surgery. In one study comparing cefazolin to other antibiotics like cefuroxime and ceftriaxone, cefazolin proved equally effective in preventing infections at the surgery site, indicating its safety for use. Another study found that a single dose of cefazolin can alter the balance of bacteria in the stomach and intestines, but this change was not associated with any serious side effects. To date, no major negative effects have been reported when using cefazolin for surgeries. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using antibiotics before surgery for melanoma because it could potentially reduce infection risks and improve recovery times. Most treatments for melanoma involve surgical resection as the standard method. However, by administering cefazolin, an antibiotic, intravenously before the surgery, there is an added layer of protection against bacterial infections, which are common concerns with surgical procedures. This approach not only aims to make surgeries safer but could also enhance overall patient outcomes by minimizing postoperative complications.

What evidence suggests that cefazolin before surgery might be effective for melanoma?

In this trial, participants in Arm A will receive cefazolin, an antibiotic, before surgical resection. Research has shown that cefazolin can affect the gut microbiome, the community of microorganisms in the intestines, in patients with early-stage melanoma. One study found that a single dose of cefazolin during surgery significantly reduced the variety of gut bacteria. This change might influence the immune system, possibly enhancing its response to surgery and cancer. While these findings are promising, further research is needed to fully understand cefazolin's impact on cancer treatment. Participants in Arm B will undergo surgical resection without cefazolin. ^{2 4 6 7 8}

Who Is on the Research Team?

Emily Z. Keung

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with early stage melanoma (stage I-II) who are scheduled for surgery to remove the cancer. Participants must not have used antibiotics in the last three months, be pregnant, or allergic to beta-lactam/cephalosporin antibiotics. They should not have infections or conditions that increase infection risk.

Inclusion Criteria

I have early stage melanoma (stage I or II).

I can sign and follow the study's consent form.

I am having surgery to remove a tumor and possibly check nearby lymph nodes.

Exclusion Criteria

I have not taken antibiotics in the three months before surgery.

I haven't taken high-dose steroids or other immune-weakening drugs in the last 2 weeks.

I have an infection at the time of my surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive cefazolin intravenously and undergo standard of care surgical resection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in microbiome and immune response post-surgery

3 months

3 visits (in-person) at 3 days, 2 weeks, and 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cefazolin
• Resection

Trial Overview The study is testing how taking the antibiotic cefazolin before surgery affects the microbiome of patients with stage I-II melanoma. Researchers want to see if changes in gut microbes influence recovery and response to cancer treatment.

How Is the Trial Designed?

Group I: Arm B (surgical resection) Experimental Treatment 1 Intervention

Patients undergo standard of care surgical resection.

Group II: Arm A (cefazolin, surgical resection) Active Control 2 Interventions

Patients receive cefazolin IV and then undergo standard of care surgical resection within 1 hour.

Resection is already approved in United States, European Union for the following indications:

Approved in United States as Surgical Resection for:

• Colorectal Cancer
• Liver Metastases
• Lung Metastases

Approved in European Union as Surgical Excision for:

• Colorectal Cancer
• Liver Metastases
• Lung Metastases

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A retrospective study of New Zealand dermatologists revealed that while dermatological surgeries in outpatient settings are generally safe, with low rates of infection (<3.5%) and bleeding (<2%), there is a need for improved preoperative and intraoperative monitoring practices.

Most dermatologists do not routinely record vital signs during procedures and often do not withhold anticoagulation or antiplatelet therapies, indicating a potential gap in safety protocols that could be addressed to enhance patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative management and the associated rate of adverse events in dermatological procedures performed by dermatologists in New Zealand. Chan, BC., Patel, DC.[2015]

In a study of 6,496 melanoma patients diagnosed between 2004 and 2012, those who underwent surgical excision within 6 weeks of diagnosis had a significantly higher 5-year overall survival rate (86%) compared to those who waited more than 90 days (78.6%).

The results suggest that timely surgical intervention is crucial for improving survival outcomes, particularly for patients with Stage 1 melanoma, highlighting the importance of prompt treatment after diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of surgical interval and survival among hospital and non-hospital based patients with melanoma in North Carolina. Adamson, AS., Jackson, BE., Baggett, CD., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04875728

NCT04875728 | The Impact of an Antibiotic (Cefazolin) ... This phase I trial investigates the impact of cefazolin before surgery on the microbiome in patients with stage I-II melanoma.

2. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/2806/735488/Abstract-2806-A-single-dose-of-perioperative

Abstract 2806: A single dose of perioperative cefazolin ... The primary objective of this study was to determine the impact of a single dose of perioperative cefazolin on the gut microbiome and immunity.

3. researchgate.net researchgate.net/publication/379198637_Abstract_2806_A_single_dose_of_perioperative_cefazolin_disrupts_the_gut_microbiome_and_immunity_in_patients_pts_with_early-stage_melanoma

A single dose of perioperative cefazolin disrupts the gut ... A pilot study in early-stage melanoma patients undergoing clean surgery found that a single dose of perioperative cefazolin significantly reduced gut ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-07071

The Impact of an Antibiotic (Cefazolin) before Surgery on ... This phase I trial investigates the impact of cefazolin before surgery on the microbiome in patients with stage I-II melanoma.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38599478/

Metronidazole and cefazolin vs cefazolin alone for surgical ... The addition of metronidazole to cefazolin before gynecologic surgery decreased the surgical site infection rate by half.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7850522/

Association of Antibiotic Exposure With Survival and ... The primary outcome was OS, and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous (IV) steroids. Deaths were ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9686604/

Meta-Analysis of Clinical Trials Comparing Cefazolin to ... Our analysis showed that cefazolin is as effective as cefuroxime, cefamandole, and ceftriaxone in preventing surgical site infections.

8. ajog.org ajog.org/article/S0002-9378(24)00507-6/fulltext

Metronidazole and cefazolin vs cefazolin alone for surgical ... The addition of metronidazole to cefazolin before gynecologic surgery decreased the surgical site infection rate by half, even after accounting ...