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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the drug rifaximin manages stomach problems caused by a specific chemotherapy treatment for breast cancer. The researchers aim to determine if rifaximin can reduce these side effects without disrupting the cancer treatment schedule. People with stage I-III HER2 positive breast cancer who experience stomach issues after starting pertuzumab-based chemotherapy might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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

Research has shown that rifaximin is generally well-tolerated by patients. Studies indicate that people taking rifaximin experience few serious side effects, suggesting it is safe for most individuals. It is already used to treat conditions like traveler's diarrhea and can help prevent certain liver issues.

One study on rifaximin for early-stage HER2 positive breast cancer reported no major side effects related to the drug. This suggests most people did not encounter significant problems when taking it.

Rifaximin might cause mild side effects like stomach pain or bloating, though these are uncommon. Overall, evidence indicates that rifaximin is a safe option for treating stomach issues caused by other cancer treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Rifaximin is unique because it targets gut bacteria to help manage gastrointestinal side effects related to breast cancer treatment, unlike standard chemotherapy drugs that focus solely on attacking cancer cells. Researchers are excited about this treatment because it offers a novel way to improve patients' quality of life by potentially reducing the uncomfortable gut issues that often accompany chemotherapy. This approach not only aims to alleviate symptoms but also supports patients in maintaining their treatment regimens without interruption.

What evidence suggests that rifaximin might be an effective treatment for gastrointestinal toxicities related to pertuzumab-based therapy?

Research shows that rifaximin might help manage stomach problems caused by pertuzumab-based chemotherapy in breast cancer patients. In this trial, participants in one arm will receive rifaximin alongside pertuzumab-based chemotherapy if they experience gastrointestinal side effects after the first cycle. Studies have found that up to 70% of patients taking pertuzumab experience digestive issues like diarrhea and stomach pain. Rifaximin has successfully reduced these side effects without causing serious problems. Earlier trials showed that patients handled rifaximin well, with no major side effects from the drug. Overall, rifaximin seems promising in making chemotherapy more comfortable by possibly easing stomach issues. ^{1 5 6 7 8}

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

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5550690/

Rifaximin for Pertuzumab-Related GI Toxicities - PMC We present a case of HER2-related therapy-induced diarrhea and abdominal pain managed successfully with Rifaximin. Keywords: HER2 positive ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e24161

Phase II trial of rifaximin in patients with early-stage HER2 ... Treatment is well tolerated, with no significant grade 3+ adverse event related to rifaximin observed. Among patients who received rifaximin, ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20478015

Rifaximin for the Treatment of Gastrointestinal Toxicities ... Rifaximin may reduce the incidence and severity of pertuzumab induced gastrointestinal toxicities without interrupting or delaying the ...

4. researchgate.net researchgate.net/publication/318984455_Rifaximin_for_Pertuzumab-Related_GI_Toxicities

Rifaximin for Pertuzumab-Related GI Toxicities Up to 70% of patients receiving pertuzumab therapy develop gastrointestinal toxicity, particularly when used with other chemotherapy agents [17] ...

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/2040622320970354

Gastrointestinal side effects of cancer treatments It is estimated that 50–80% of patients develop chemotherapy-induced diarrhoea with 30% of patients developing a grade 3 [common terminology ...

6. rxlist.com rxlist.com/xifaxan-drug.htm

Xifaxan (Rifaximin): Side Effects, Uses, Dosage ... diarrhea that is watery or bloody (even if it occurs months after your last dose),. fever,; rapid weight gain,; stomach pain,; bloating, and; trouble breathing.

7. my.clevelandclinic.org my.clevelandclinic.org/health/drugs/18573-rifaximin-tablets

Rifaximin (Xifaxan): Uses & Side Effects Rifaximin (Xifaxan) treats diarrhea caused by traveling or irritable bowel syndrome. It can also prevent hepatic encephalopathy.

8. mayoclinic.org mayoclinic.org/drugs-supplements/rifaximin-oral-route/description/drg-20065817

Rifaximin (oral route) - Side effects & dosage Rifaximin is used to treat traveler's diarrhea that is caused by a bacteria called Escherichia coli. It is also used to prevent hepatic encephalopathy.