Rifaximin for the Treatment of Gastrointestinal Toxicities Related to Pertuzumab-Based Therapy in Patients With Stage I-III HER2 Positive Breast Cancer

NCT04249622 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: MC18C3NCI-2020-0033218-009108
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; HER2 Positive Breast Carcinoma; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Reduction Rate of >= Grade 2 Abdominal Toxicities Including Abdominal Distension, Abdominal Pain, Diarrhea, Dyspepsia, Stomach Pain, and Typhlitis

  Based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner (1987).

  Through study completion (approximately 2 years, 3 months)

Secondary Outcomes (5)

• Dose Reductions of Treatment With Pertuzumab

  Up to 3 years

• Dose Delays of Treatment With Pertuzumab

  Up to 3 years

• Discontinuation of Treatment With Pertuzumab

  Up to 3 years

• Number of Patient With a Reduction of Mean Number of Stools

  Up to 3 years

• Average Maximum Pertuzumab Induced Gastrointestinal Toxicities (PIGT) Score

  Baseline (at enrollment); following each treatment cycle (21 days +/- 7 days), up to 5 cycles

Other Outcomes (3)

• Changes in the Fecal Microbiome, Hydrogen Breath Test, and Permeability Test - Rifaximin

  Baseline up to 3 years

• Changes in the Fecal Microbiome, Hydrogen Breath Test, and Permeability Test - Pertuzumab

  Baseline up to 3 years

• Difference in the Fecal Microbiome, Hydrogen Breath Test, and Permeability Test

  Up to 3 years

Study Arms (2)

Arm I (rifaximin, pertuzumab-based chemotherapy)

EXPERIMENTAL

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.

Other: Best Practice; Other: Questionnaire Administration; Drug: Rifaximin

Arm II (pertuzumab-based chemotherapy)

ACTIVE COMPARATOR

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.

Other: Best Practice; Other: Questionnaire Administration

Interventions

Best Practice OTHER

Given standard of care pertuzumab-based chemotherapy

Also known as: standard of care, standard therapy

Arm I (rifaximin, pertuzumab-based chemotherapy); Arm II (pertuzumab-based chemotherapy)

Questionnaire Administration OTHER

Ancillary studies

Arm I (rifaximin, pertuzumab-based chemotherapy); Arm II (pertuzumab-based chemotherapy)

Rifaximin DRUG

Given PO

Also known as: Xifaxan

Arm I (rifaximin, pertuzumab-based chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years
• Histological confirmation of HER2 positive breast cancer stage I-III per American Joint Committee on Cancer (AJCC) staging 8th edition
• Provide written informed consent
• Breast cancer patients who will be receiving pertuzumab-based chemotherapy with either TCHP (docetaxel, carboplatin, trastuzumab, and pertuzumab) or docetaxel/paclitaxel, trastuzumab, and pertuzumab
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Hemoglobin \>= 10.0 g/dL (obtained =\< 30 days prior to pre-registration)
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (obtained =\< 30 days prior to pre-registration)
• Platelet count \>= 100 x 10\^9/L (obtained =\< 30 days prior to pre-registration)
• Total bilirubin =\< 1.5 x ULN (institutional upper limit of normal) (obtained =\< 30 days prior to pre-registration)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (obtained =\< 30 days prior to pre-registration)
• Serum or plasma creatinine =\< 1.5 x ULN (obtained =\< 30 days prior to pre-registration)
• Calculated creatinine clearance \>= 45 ml/min using the Cockcroft-Gault formula (obtained =\< 30 days prior to pre-registration)
• Negative serum pregnancy test done =\< 30 days prior to pre-registration, for person of childbearing potential only
• Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Willingness to provide mandatory stool specimen for correlative research

You may not qualify if:

• History of myocardial infarction =\< 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment
• EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment
• Uncontrolled intercurrent non-cardiac illness including, but not limited to:
• Ongoing or active infection
• Psychiatric illness/social situations
• Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
• Any other conditions that would limit compliance with study requirements
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
• NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm (adjust to protocol if applicable)
• Any of the following because this study involves an agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
• Pregnant women
• Nursing women
• Women of childbearing potential who are unwilling to employ adequate contraception

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

Practice Guidelines as Topic; Standard of Care; Rifaximin

Intervention Hierarchy (Ancestors)

Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality Indicators, Health Care; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Saranya Chumsri, MD
• Organization: Mayo Clinic

Chumsri.Saranya@mayo.edu

904-953-2000

Study Officials

• Saranya Chumsri, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: January 31, 2020
• Study Start: September 18, 2020
• Primary Completion: December 27, 2022
• Study Completion: December 27, 2022
• Last Updated: September 16, 2025
• Results First Posted: August 7, 2025

Record last verified: 2025-08

Locations

US (1)