Rifaximin for the Treatment of Gastrointestinal Toxicities Related to Pertuzumab-Based Therapy in Patients With Stage I-III HER2 Positive Breast Cancer
Keywords
Abstract
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.
Dates
| Last Verified: | 12/31/2019 |
| First Submitted: | 01/26/2020 |
| Estimated Enrollment Submitted: | 01/27/2020 |
| First Posted: | 01/30/2020 |
| Last Update Submitted: | 06/11/2020 |
| Last Update Posted: | 06/15/2020 |
| Actual Study Start Date: | 07/31/2020 |
| Estimated Primary Completion Date: | 02/28/2023 |
| Estimated Study Completion Date: | 02/28/2023 |
Condition or disease
Intervention/treatment
Other: Best Practice
Other: Questionnaire Administration
Drug: Arm I (rifaximin, pertuzumab-based chemotherapy)
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: 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. | Drug: Arm I (rifaximin, pertuzumab-based chemotherapy) Given PO |
| Active Comparator: 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. |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - PRE-REGISTRATION INCLUSION CRITERIA - 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, 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 and urine specimen for correlative research - Ability to complete questionnaire(s) by themselves or with assistance - REGISTRATION INCLUSION CRITERIA - Receiving pertuzumab based regimens in the adjuvant or neoadjuvant setting with pertuzumab dose of 840 mg - Hemoglobin >= 10.0 g/dL (obtained =< 7 days prior to registration) - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained =< 7 days prior to registration) - Platelet count >= 100 x 10^9/L (obtained =< 7 days prior to registration) - Total bilirubin =< 1.5 x ULN (institutional upper limit of normal) (obtained =< 7 days prior to registration) - AST (SGOT)/ALT (SGPT) =< 2.5 x ULN (obtained =< 7 days prior to registration) - Serum or plasma creatinine =< 1.5 x ULN (obtained =< 7 days prior to registration) - Calculated creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula (obtained =< 7 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 |
Outcome
Primary Outcome Measures
1. Reduction rate of >= grade 2 abdominal toxicities including abdominal distension, abdominal pain, diarrhea, dyspepsia, stomach pain, and typhlitis [Up to 3 years]
Secondary Outcome Measures
1. Dose reductions of treatment with pertuzumab [Up to 3 years]
2. Dose delays of treatment with pertuzumab [Up to 3 years]
3. Discontinuation of treatment with pertuzumab [Up to 3 years]
4. Change in the Bristol stool scale before and after rifaximin treatment [Baseline up to 3 years]
5. Other pertuzumab induced gastrointestinal toxicities (PIGT) such as abdominal pain, bloating and flatulence [Up to 3 years]
Other Outcome Measures
1. Changes in the fecal microbiome [Baseline up to 3 years]
2. Changes in the hydrogen breath test [Baseline up to 3 years]
3. Difference in the fecal microbiome test [Up to 3 years]
4. Difference in the hydrogen breath test [Up to 3 years]
5. Difference in the permeability test [Up to 3 years]
