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

Primary Purpose

Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Best Practice
Questionnaire Administration
Rifaximin
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anatomic Stage I Breast Cancer AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • PRE-REGISTRATION INCLUSION CRITERIA
  • 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
  • Ability to complete questionnaire(s) by themselves or with assistance
  • REGISTRATION INCLUSION CRITERIA
  • Received pertuzumab based regimens in the adjuvant or neoadjuvant setting
  • Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained =< 14 days prior to registration)
  • Platelet count >= 100 x 10^9/L (obtained =< 14 days prior to registration)
  • Total bilirubin =< 1.5 x ULN (institutional upper limit of normal) (obtained =< 14 days prior to registration)
  • AST (SGOT)/ALT (SGPT) =< 2.5 x ULN (obtained =< 14 days prior to registration)
  • Serum or plasma creatinine =< 1.5 x ULN (obtained =< 14 days prior to registration)
  • Calculated creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula (obtained =< 14 days prior to registration)

Exclusion Criteria:

  • PRE-REGISTRATION EXCLUSION CRITERIA
  • 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
  • Current colostomy or ileostomy
  • History of inflammatory bowel disease
  • History of irritable bowel syndrome
  • History of arteriovenous malformations
  • History of gastrointestinal bleeds
  • Previous surgical resection of the small bowel or colon
  • Previous allergy to rifaximin or its derivatives

Sites / Locations

  • Mayo Clinic in Florida

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (rifaximin, pertuzumab-based chemotherapy)

Arm II (pertuzumab-based chemotherapy)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Reduction rate of >= grade 2 abdominal toxicities including abdominal distension, abdominal pain, diarrhea, dyspepsia, stomach pain, and typhlitis
Based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). 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).

Secondary Outcome Measures

Dose reductions of treatment with pertuzumab
Descriptive statistics (frequency table) and histogram will be used to summarize dose reductions, dose delays and discontinuation of treatment with pertuzumab due to gastrointestinal side effects.
Dose delays of treatment with pertuzumab
Descriptive statistics (frequency table) and histogram will be used to summarize dose reductions, dose delays and discontinuation of treatment with pertuzumab due to gastrointestinal side effects.
Discontinuation of treatment with pertuzumab
Descriptive statistics (frequency table) and histogram will be used to summarize dose reductions, dose delays and discontinuation of treatment with pertuzumab due to gastrointestinal side effects.
Change in the Bristol stool scale before and after rifaximin treatment
Descriptive statistics (frequency table) and histogram will be used to summarize the Bristol stool scale during the study.
Other pertuzumab induced gastrointestinal toxicities (PIGT) such as abdominal pain, bloating and flatulence
Descriptive statistics (frequency table) and histogram will be used to summarize other PIGT such as abdominal pain, bloating and flatulence as measured by a 4 point Likert scale during the study.

Full Information

First Posted
January 27, 2020
Last Updated
October 16, 2023
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04249622
Brief Title
Rifaximin for the Treatment of Gastrointestinal Toxicities Related to Pertuzumab-Based Therapy in Patients With Stage I-III HER2 Positive Breast Cancer
Official Title
Phase II Trial of Rifaximin in Patients With Early Stage HER2 Positive Breast Cancer With Gastrointestinal Toxicities Related to Pertuzumab-Based Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 18, 2020 (Actual)
Primary Completion Date
December 27, 2022 (Actual)
Study Completion Date
December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the reduction rate of grade >= 2 abdominal toxicities, including abdominal distension, abdominal pain, diarrhea, dyspepsia, stomach pain, and typhlitis according to the National Cancer Institute Common Terminology for Adverse Events version 5.0 (NCI CTCAE v5.0) with the use of rifaximin in stage II-III HER-2 positive breast cancer patients with pertuzumab induced gastrointestinal toxicities. SECONDARY OBJECTIVES: I. Evaluate dose reductions, dose delays and discontinuation of treatment with pertuzumab due to gastrointestinal side effects. II. Evaluate and measure the change in the Bristol stool scale before and after rifaximin treatment. III. Evaluate and measure the change in the 4-point Likert scale patient questionnaire before and after rifaximin treatment. CORRELATIVE STUDY OBJECTIVES: I. Evaluate changes in the fecal microbiome, hydrogen breath test, and permeability test before and after rifaximin. II. Evaluate changes in the fecal microbiome, hydrogen breath test, and permeability test before and after pertuzumab-based chemotherapy. III. Evaluate the difference in the fecal microbiome, hydrogen breath test, and permeability test among patients with or without pertuzumab induced gastrointestinal toxicities (PIGT). OUTLINE: Patients are assigned to 1 of 2 arms. ARM I (GRADE >= 2 PIGT): Patients that experience PIGT after receiving first standard of care cycle of pertuzumab-based chemotherapy receive rifaximin orally (PO) twice daily (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. ARM II (GRADE =< 1 PIGT): 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (rifaximin, pertuzumab-based chemotherapy)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II (pertuzumab-based chemotherapy)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Best Practice
Other Intervention Name(s)
standard of care, standard therapy
Intervention Description
Given standard of care pertuzumab-based chemotherapy
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Intervention Type
Drug
Intervention Name(s)
Rifaximin
Other Intervention Name(s)
Xifaxan
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Reduction rate of >= grade 2 abdominal toxicities including abdominal distension, abdominal pain, diarrhea, dyspepsia, stomach pain, and typhlitis
Description
Based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). 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).
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Dose reductions of treatment with pertuzumab
Description
Descriptive statistics (frequency table) and histogram will be used to summarize dose reductions, dose delays and discontinuation of treatment with pertuzumab due to gastrointestinal side effects.
Time Frame
Up to 3 years
Title
Dose delays of treatment with pertuzumab
Description
Descriptive statistics (frequency table) and histogram will be used to summarize dose reductions, dose delays and discontinuation of treatment with pertuzumab due to gastrointestinal side effects.
Time Frame
Up to 3 years
Title
Discontinuation of treatment with pertuzumab
Description
Descriptive statistics (frequency table) and histogram will be used to summarize dose reductions, dose delays and discontinuation of treatment with pertuzumab due to gastrointestinal side effects.
Time Frame
Up to 3 years
Title
Change in the Bristol stool scale before and after rifaximin treatment
Description
Descriptive statistics (frequency table) and histogram will be used to summarize the Bristol stool scale during the study.
Time Frame
Baseline up to 3 years
Title
Other pertuzumab induced gastrointestinal toxicities (PIGT) such as abdominal pain, bloating and flatulence
Description
Descriptive statistics (frequency table) and histogram will be used to summarize other PIGT such as abdominal pain, bloating and flatulence as measured by a 4 point Likert scale during the study.
Time Frame
Up to 3 years
Other Pre-specified Outcome Measures:
Title
Changes in the fecal microbiome, hydrogen breath test, and permeability test - rifaximin
Description
Descriptive statistics (mean, standard deviation [sd], median, interquartile range [iqr]) and longitudinal plots (raw value, change, change in percentage) will be used to summarize the baseline levels of hydrogen/methane peak by hydrogen breath test , diversity of gut microbiome(number of species) and specific species by fecal microbiome, and levels of urine mannitol and lactulose by permeability test before and after rifaximin.
Time Frame
Baseline up to 3 years
Title
Changes in the fecal microbiome, hydrogen breath test, and permeability test - pertuzumab
Description
Descriptive statistics (mean, sd, median, iqr) and longitudinal plots (raw value, change, change in percentage) will be used to summarize the baseline levels of hydrogen/methane peak by hydrogen breath test, diversity of gut microbiome (number of species) and specific species by fecal microbiome, and levels of urine mannitol and lactulose by permeability test before and after pertuzumab-based chemotherapy.
Time Frame
Baseline up to 3 years
Title
Difference in the fecal microbiome, hydrogen breath test, and permeability test
Description
Descriptive statistics (mean, sd, median, iqr) and longitudinal plots (raw value, change, change in percentage) will be used to the fecal microbiome, hydrogen breath test, and permeability test among patients with or without PIGT. The study is not powered to detect any differences between the two arms; the main purpose is to quantify and evaluate differences descriptively between patients who develop and do not develop PIGT (between arm 1 and arm 2) to inform subsequent research.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: PRE-REGISTRATION INCLUSION CRITERIA 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 Ability to complete questionnaire(s) by themselves or with assistance REGISTRATION INCLUSION CRITERIA Received pertuzumab based regimens in the adjuvant or neoadjuvant setting Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration) Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained =< 14 days prior to registration) Platelet count >= 100 x 10^9/L (obtained =< 14 days prior to registration) Total bilirubin =< 1.5 x ULN (institutional upper limit of normal) (obtained =< 14 days prior to registration) AST (SGOT)/ALT (SGPT) =< 2.5 x ULN (obtained =< 14 days prior to registration) Serum or plasma creatinine =< 1.5 x ULN (obtained =< 14 days prior to registration) Calculated creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula (obtained =< 14 days prior to registration) Exclusion Criteria: PRE-REGISTRATION EXCLUSION CRITERIA 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 Current colostomy or ileostomy History of inflammatory bowel disease History of irritable bowel syndrome History of arteriovenous malformations History of gastrointestinal bleeds Previous surgical resection of the small bowel or colon Previous allergy to rifaximin or its derivatives
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saranya Chumsri, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

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

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