Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, HER2 Positive Breast Carcinoma, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8
Conditions
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.
Interventions
Given standard of care pertuzumab-based chemotherapy
Ancillary studies
Given PO
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction Rate of >= Grade 2 Abdominal Toxicities Including Abdominal Distension, Abdominal Pain, Diarrhea, Dyspepsia, Stomach Pain, and Typhlitis | Through study completion (approximately 2 years, 3 months) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Delays of Treatment With Pertuzumab | Up to 3 years | Number of patients that experienced a dose delay with pertuzumab due to gastrointestinal side effects. |
| Discontinuation of Treatment With Pertuzumab | Up to 3 years | The number of patients that experienced discontinuation of treatment with pertuzumab due to gastrointestinal side effects. |
| Number of Patient With a Reduction of Mean Number of Stools | Up to 3 years | Number of patients that experienced a reduction of mean number of stools recorded while on treatment compared to baseline will be reported |
| Average Maximum Pertuzumab Induced Gastrointestinal Toxicities (PIGT) Score | Baseline (at enrollment); following each treatment cycle (21 days +/- 7 days), up to 5 cycles | Maximum PIGT score represents the maximum grade of adverse event experienced by a patient out of all gastrointestinal adverse events. PIGT scores are assessed according to NCI CTCAE v5.0, with a minimum grade of 0 (no event) and maximum grade of 5 (death). |
| Dose Reductions of Treatment With Pertuzumab | Up to 3 years | Number of patients that experienced a dose reductions with pertuzumab due to gastrointestinal side effects. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Difference in the Fecal Microbiome, Hydrogen Breath Test, and Permeability Test | Up to 3 years | 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. |
| Changes in the Fecal Microbiome, Hydrogen Breath Test, and Permeability Test - Pertuzumab | Baseline up to 3 years | 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. |
| Changes in the Fecal Microbiome, Hydrogen Breath Test, and Permeability Test - Rifaximin | Baseline up to 3 years | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) 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.\>
* Best Practice: Given standard of care pertuzumab-based chemotherapy \>
* Questionnaire Administration: Ancillary studies \>
* Rifaximin: Given PO | 18 |
| Arm II (Pertuzumab-based Chemotherapy) 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.\>
* Best Practice: Given standard of care pertuzumab-based chemotherapy\>
* Questionnaire Administration: Ancillary studies | 2 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Alternative therapy | 1 | 0 |
| Overall Study | Discontinuation of pertuzumab | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Arm II (Pertuzumab-based Chemotherapy) |
|---|---|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 9.35 | 53.8 years STANDARD_DEVIATION 9.72 | 55.0 years STANDARD_DEVIATION 7.07 |
| ECOG Performance Status 0 | 18 Participants | 16 Participants | 2 Participants |
| ECOG Performance Status 1 | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 16 Participants | 2 Participants |
| Region of Enrollment United States | 20 participants | 18 participants | 2 participants |
| Sex: Female, Male Female | 20 Participants | 18 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 2 |
| other Total, other adverse events | 18 / 18 | 2 / 2 |
| serious Total, serious adverse events | 1 / 18 | 0 / 2 |
Outcome results
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).
Time frame: Through study completion (approximately 2 years, 3 months)
Population: Only patients that received rifaximin were included in analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Reduction Rate of >= Grade 2 Abdominal Toxicities Including Abdominal Distension, Abdominal Pain, Diarrhea, Dyspepsia, Stomach Pain, and Typhlitis | 0.833 proportion of participants |
Average Maximum Pertuzumab Induced Gastrointestinal Toxicities (PIGT) Score
Maximum PIGT score represents the maximum grade of adverse event experienced by a patient out of all gastrointestinal adverse events. PIGT scores are assessed according to NCI CTCAE v5.0, with a minimum grade of 0 (no event) and maximum grade of 5 (death).
Time frame: Baseline (at enrollment); following each treatment cycle (21 days +/- 7 days), up to 5 cycles
Population: Only patients in arm 1 were included in analysis. Patients in arm 2 did not experience PIGT. Only patients still on treatment were included in each cycle's analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Average Maximum Pertuzumab Induced Gastrointestinal Toxicities (PIGT) Score | Baseline | 2.17 units on a scale | Standard Deviation 0.38 |
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Average Maximum Pertuzumab Induced Gastrointestinal Toxicities (PIGT) Score | Cycle 1 | 1.61 units on a scale | Standard Deviation 0.78 |
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Average Maximum Pertuzumab Induced Gastrointestinal Toxicities (PIGT) Score | Cycle 2 | 1.83 units on a scale | Standard Deviation 0.79 |
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Average Maximum Pertuzumab Induced Gastrointestinal Toxicities (PIGT) Score | Cycle 3 | 1.71 units on a scale | Standard Deviation 0.85 |
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Average Maximum Pertuzumab Induced Gastrointestinal Toxicities (PIGT) Score | Cycle 4 | 1.5 units on a scale | Standard Deviation 0.73 |
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Average Maximum Pertuzumab Induced Gastrointestinal Toxicities (PIGT) Score | Cycle 5 | 1.53 units on a scale | Standard Deviation 0.74 |
Discontinuation of Treatment With Pertuzumab
The number of patients that experienced discontinuation of treatment with pertuzumab due to gastrointestinal side effects.
Time frame: Up to 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Discontinuation of Treatment With Pertuzumab | 0 Participants |
| Arm II (Pertuzumab-based Chemotherapy) | Discontinuation of Treatment With Pertuzumab | 0 Participants |
Dose Delays of Treatment With Pertuzumab
Number of patients that experienced a dose delay with pertuzumab due to gastrointestinal side effects.
Time frame: Up to 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Dose Delays of Treatment With Pertuzumab | 1 Participants |
| Arm II (Pertuzumab-based Chemotherapy) | Dose Delays of Treatment With Pertuzumab | 0 Participants |
Dose Reductions of Treatment With Pertuzumab
Number of patients that experienced a dose reductions with pertuzumab due to gastrointestinal side effects.
Time frame: Up to 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Dose Reductions of Treatment With Pertuzumab | 10 Participants |
| Arm II (Pertuzumab-based Chemotherapy) | Dose Reductions of Treatment With Pertuzumab | 0 Participants |
Number of Patient With a Reduction of Mean Number of Stools
Number of patients that experienced a reduction of mean number of stools recorded while on treatment compared to baseline will be reported
Time frame: Up to 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Rifaximin, Pertuzumab-based Chemotherapy) | Number of Patient With a Reduction of Mean Number of Stools | 7 Participants |
| Arm II (Pertuzumab-based Chemotherapy) | Number of Patient With a Reduction of Mean Number of Stools | 0 Participants |
Changes in the Fecal Microbiome, Hydrogen Breath Test, and Permeability Test - Pertuzumab
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
Changes in the Fecal Microbiome, Hydrogen Breath Test, and Permeability Test - Rifaximin
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
Difference in the Fecal Microbiome, Hydrogen Breath Test, and Permeability Test
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