Rifaximin for Breast Cancer-Related Gastrointestinal Side Effects

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Pertuzumab

Must not be taking: Antiretrovirals

Disqualifiers: Myocardial infarction, Congestive heart failure, Inflammatory bowel disease, Irritable bowel syndrome, 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: 15 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies how well rifaximin works for the treatment of gastrointestinal toxicities related to pertuzumab-based therapy in patients with stage I-III HER2 positive breast cancer. Rifaximin may reduce the incidence and severity of pertuzumab induced gastrointestinal toxicities without interrupting or delaying the chemotherapy schedule.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is rifaximin generally safe for human use?

Rifaximin is a non-absorbable antibiotic that has been used safely for various gastrointestinal conditions, including travelers' diarrhea and hepatic encephalopathy. It is known for its minimal absorption in the body, which reduces the risk of systemic side effects, and it has been used since 1987 in many countries with a good safety profile. ^{1 2 3 4 5}

How does the drug Rifaximin differ from other treatments for breast cancer-related gastrointestinal side effects?

Rifaximin is unique because it is an antibiotic that works by altering the gut bacteria, which may help manage gastrointestinal side effects related to breast cancer treatment. Unlike other treatments that might focus on directly targeting cancer cells or managing symptoms through different mechanisms, Rifaximin's approach is through modifying the gut microbiome. ^{6 7 8 9 10}

Who Is on the Research Team?

Saranya Chumsri, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults with stage I-III HER2 positive breast cancer who are receiving pertuzumab-based chemotherapy. They must have normal liver and kidney function, stable blood counts, and no history of significant gastrointestinal issues or recent heart attacks. Pregnant women, nursing mothers, those with certain illnesses or on antiretroviral therapy for HIV cannot participate.

Inclusion Criteria

Your kidneys work well enough, with a specific level of creatinine clearance.

Provide written informed consent

I have been treated with pertuzumab for my cancer before surgery or as an initial treatment.

Exclusion Criteria

You have had an allergic reaction to rifaximin or similar medicines in the past.

I still have side effects from my last cancer treatment.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rifaximin and pertuzumab-based chemotherapy. Rifaximin is administered orally twice daily on days 1-5, and chemotherapy is given on day 1. Treatment repeats every 21 days for up to 5 cycles.

15 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in the fecal microbiome, hydrogen breath test, and permeability test.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Rifaximin

Trial Overview The trial is testing if rifaximin can reduce gastrointestinal side effects caused by pertuzumab-based therapy in breast cancer patients without delaying their treatment schedule. Participants will also complete questionnaires to provide additional data.

How Is the Trial Designed?

Group I: Arm I (rifaximin, pertuzumab-based chemotherapy) Experimental Treatment 3 Interventions

Patients that experience PIGT after receiving first standard of care cycle of pertuzumab-based chemotherapy receive rifaximin PO BID on days 1-5 and standard of care pertuzumab-based chemotherapy on day 1. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (pertuzumab-based chemotherapy) Active Control 2 Interventions

Patients that do not experience PIGT after receiving first standard of care cycle of pertuzumab-based chemotherapy continue receiving standard of care pertuzumab-based chemotherapy on day 1. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Rifaximin is effective in treating travelers' diarrhea caused by Escherichia coli, showing similar efficacy to ciprofloxacin, but it does not work against Campylobacter jejuni infections.

Beyond travelers' diarrhea, rifaximin has potential uses in treating various gastrointestinal disorders, including hepatic encephalopathy and Crohn's disease, due to its broad spectrum of activity and poor absorption in the gastrointestinal tract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin: a nonabsorbed oral antibiotic. Baker, DE.[2018]

Trastuzumab deruxtecan (T-DXd) is a promising HER2-targeted therapy that has shown significant anti-tumor activity in heavily pre-treated patients with HER2-positive breast and gastric cancers, and preliminary data suggest it may also be effective in HER2-positive non-small cell lung cancer (NSCLC) and colorectal cancer.

While T-DXd has an acceptable safety profile, there are concerns about serious treatment-emergent adverse events, highlighting the need for careful monitoring in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors. Indini, A., Rijavec, E., Grossi, F.[2021]

Trastuzumab deruxtecan (T-DXd) has shown significant antitumor activity in patients with HER2-positive advanced gastric cancer (AGC) who have previously undergone at least two therapies, leading to its approval in Japan and by the US FDA.

The treatment resulted in a higher objective response rate and longer overall survival compared to previous therapies, with an acceptable safety profile, indicating its potential as an effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan for the treatment of HER2-positive gastric cancer. Mishima, S., Shitara, K.[2022]

Citations

1. Greece pubmed.ncbi.nlm.nih.gov

Rifaximin, a non-absorbable antibiotic, inhibits the release of pro-angiogenic mediators in colon cancer cells through a pregnane X receptor-dependent pathway. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Rifaximin: a nonabsorbed oral antibiotic. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Pregnane-X-receptor mediates the anti-inflammatory activities of rifaximin on detoxification pathways in intestinal epithelial cells. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Activation of intestinal human pregnane X receptor protects against azoxymethane/dextran sulfate sodium-induced colon cancer. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Rifaximin: beyond the traditional antibiotic activity. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors. [2021]

7. England pubmed.ncbi.nlm.nih.gov

The emergence of targeted therapy for HER2-low triple-negative breast cancer: a review of fam-trastuzumab deruxtecan. [2023]

8. Japan pubmed.ncbi.nlm.nih.gov

[A Patient with HER2-Positive Stage IV Advanced Gastric Cancer Who Received Chemotherapy with Trastuzumab plus XP Followed by Conversion Surgery]. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan for the treatment of HER2-positive gastric cancer. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Trastuzumab Deruxtecan in Breast Cancer: A Systematic Review and Meta-Analysis. [2023]