Antibiotics + Chemotherapy for Colorectal Cancer

Overseen By Massey Investigator-Initiated Trials Research Operations Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Virginia Commonwealth University

Must not be taking: Disulfiram, Tizanidine, Theophylline, others

Disqualifiers: Anticoagulation, Total colectomy, Cockayne, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

97 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding a combination of antibiotics (ciprofloxacin and metronidazole) and aspirin to standard chemotherapy can improve treatment outcomes for people with stage IV colorectal cancer. It includes two groups: one receiving chemotherapy alone, and the other receiving the added antibiotics and aspirin to determine if it enhances cancer treatment. Individuals diagnosed with stage IV colorectal cancer and set to begin their first-line chemotherapy might be suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires you to stop taking disulfiram, tizanidine, or theophylline for the length of the microbiome modulation therapy. If you are on full dose anticoagulation, you may need to lower the dose by half before starting the study drugs. If you are taking methotrexate at doses of 15 mg/week or more, you cannot participate in the trial.

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

Previous studies have shown that aspirin reduces the risk of colorectal cancer returning by 55%. This suggests it is well-tolerated by many patients and could be safe to use. Metronidazole has also lowered the chance of cancer spreading to the liver after colorectal cancer surgery. When combined with metronidazole and aspirin, ciprofloxacin might help reduce cancer-related bacteria when given with standard chemotherapy.

As this trial enters its second phase, some safety information is available, but further testing will ensure its safety and effectiveness for patients. These results suggest the treatment could be safe, but more information will be gathered during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of antibiotics and standard chemotherapy for colorectal cancer because it introduces a novel approach by modulating the gut microbiome. This treatment adds metronidazole, ciprofloxacin, and aspirin to the usual chemotherapy regimen, aiming to enhance its effectiveness. Unlike traditional treatments like FOLFOX or FOLFIRI, which primarily target cancer cells directly, this method potentially improves patient response by altering the gut bacteria, which might play a role in cancer progression. This innovative angle of targeting the microbiome is what sets this treatment apart and holds promise for better outcomes.

What evidence suggests that this trial's treatments could be effective for stage IV colorectal cancer?

In this trial, one group of participants will receive a combination of metronidazole, ciprofloxacin, and aspirin alongside standard chemotherapy to explore potential benefits for treating stage IV colorectal cancer. Research has shown that metronidazole can reduce the chance of cancer spreading to the liver after surgery. Ciprofloxacin and metronidazole may also decrease harmful bacteria linked to cancer. Studies have found that low-dose aspirin can lower the risk of colorectal cancer returning in some patients. Specifically, one study showed that people taking aspirin had a slightly better chance of being cancer-free after five years compared to those who did not take it. ^{1 4 5 6 7}

Who Is on the Research Team?

Emily Kinsey, MD

Principal Investigator

Virginia Commonwealth University

Are You a Good Fit for This Trial?

This trial is for individuals with stage IV colorectal cancer. Participants should be starting their first chemotherapy treatment. The trial excludes those who have had previous treatments for CRC, are allergic to the antibiotics or aspirin being tested, or have other health conditions that could interfere with the study.

Inclusion Criteria

* Diagnosis of stage IV colorectal cancer

* Measurable disease by Response evaluation criteria in solid tumors (RECIST) 1.1 criteria

* Planned first-line treatment with a 5FU-based doublet chemotherapy regimen for colon cancer, specifics of the regimen at the discretion of the treating physician Note: Patients who have received adjuvant therapy \>6 months prior are eligible

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard of care chemotherapy with or without MBMT, including metronidazole, ciprofloxacin, and aspirin for 28 days

28 days

Bi-weekly visits for chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival and progression-free survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin
• Ciprofloxacin
• Metronidazole
• Standard of Care Chemotherapy

Trial Overview The study is testing if adding antibiotics (ciprofloxacin and metronidazole) and aspirin to standard chemotherapy improves outcomes in stage IV colorectal cancer patients. It's a phase 2 trial with two groups: one receiving just chemo, and the other getting chemo plus these additional medications.

How Is the Trial Designed?

Group I: Metronidazole Ciprofloxacin and Aspirin Therapy Experimental Treatment 1 Intervention

First line chemo therapy (standard of care) + Microbiome modulation therapy MBMT 500 mg metronidazole 3 times daily, 500 mg ciprofloxacin twice daily, and 81 mg aspirin once daily for 28 days

Group II: Standard of care Active Control 1 Intervention

First line chemotherapy as directed. Standard of care chemotherapy treatment options include but are not limited to the following: * FOLFOX every 2 weeks * FOLFIRI every 2 weeks * FOLFOX + bevacizumab or panitumumab every 2 weeks * FOLFIRI + bevacizumab or panitumumab every 2 weeks * CAPEOX every 3 weeks * CAPEOX + bevacizumab or panitumumab every 3 weeks

Standard of Care Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Various cancers including breast, lung, colon, pancreatic, and others

Approved in United States as Chemotherapy for:

• Various cancers including breast, lung, colon, pancreatic, and others

Approved in Canada as Chemotherapy for:

• Various cancers including breast, lung, colon, pancreatic, and others

Approved in Japan as Chemotherapy for:

• Various cancers including breast, lung, colon, pancreatic, and others

Approved in China as Chemotherapy for:

• Various cancers including breast, lung, colon, pancreatic, and others

Approved in Switzerland as Chemotherapy for:

• Various cancers including breast, lung, colon, pancreatic, and others

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

American Cancer Society, Inc.

Collaborator

Trials

237

Recruited

110,000+

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-10463

Ciprofloxacin, Metronidazole, and Aspirin with Standard of ... Ciprofloxacin, metronidazole and aspirin may reduce the amount of cancer-associated bacteria and, when given with first-line standard of care chemotherapy, may ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10841309/

The Comparative Effectiveness of Ciprofloxacin and ... We demonstrated no significant difference in the real-world effectiveness of ciprofloxacin, metronidazole, or combination therapy for the initial episode of ...

3. asco.org asco.org/about-asco/press-center/news-releases/new-findings-aspirin-and-risk-colorectal-cancer-recurrence

Aspirin May Reduce Risk of Colorectal Cancer Recurrence ... A simple intervention of low-dose aspirin reduces the risk of colorectal cancer recurrence for patients with genetic changes in the PI3K signaling pathway.

4. cancerhealth.com cancerhealth.com/article/can-aspirin-improve-colorectal-cancer-outcomes

Can Aspirin Improve Colorectal Cancer Outcomes? At five years, disease-free survival rates were 77.0% in the aspirin group versus 74.8% in the placebo group. This reflects a 9% lower risk of ...

5. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07628-y

A prospective, single-centre, randomized, double-blind ... - Trials ... metronidazole can effectively reduce the incidence of postoperative liver metastasis in patients with colorectal cancer. Rui Qi Gao ORCID ...

6. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2816726

Morbidity After Mechanical Bowel Preparation and Oral ... Findings of this randomized clinical trial indicate that MOABP reduced overall postoperative complications as well as rates of SSIs and anastomotic dehiscences.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6741347/

Aspirin and colorectal cancer: the promise of precision ... Several decades of research have provided considerable evidence demonstrating its potential for the prevention of cancer, particularly colorectal cancer.