Diarrhea Prevention and Prophylaxis With Crofelemer in HER2 Positive Breast Cancer Patients
Keywords
Abstract
Description
Various anti-diarrheal agents, such as loperamide, codeine, octreotide, are available for diarrhea management, but few are used in the prophylactic setting and none provide a targeted approach for treating chemotherapy induced diarrhea (CID).
Pre-clinical studies have suggested that blocking EGFR results in excess chloride secretion and thus diarrhea. Crofelemer is an extract from the blood red bark of Croton lechleri that inhibits luminal chloride efflux by blocking the calcium activated chloride channel (CaCC) and cystic fibrosis transmembrane regulator (CFTR) chloride channels. Due to its size and polarity, it acts only luminally and is not systemically absorbed. It is currently FDA approved for use in preventing diarrhea in HIV/AIDS patients on anti-retroviral therapy.
Dates
| Last Verified: | 02/29/2020 |
| First Submitted: | 09/18/2016 |
| Estimated Enrollment Submitted: | 09/18/2016 |
| First Posted: | 09/20/2016 |
| Last Update Submitted: | 03/03/2020 |
| Last Update Posted: | 03/05/2020 |
| Actual Study Start Date: | 01/30/2017 |
| Estimated Primary Completion Date: | 05/31/2020 |
| Estimated Study Completion Date: | 05/31/2020 |
Condition or disease
Intervention/treatment
Drug: Treatment
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Treatment Patients on the treatment arm will take one tablet of crofelemer twice a day (each tablet is 125 mg), to be swallowed whole without chewing or crushing, during cycles 1-2 of chemotherapy with THP or TCHP. Patient will be monitored off crofelemer during cycle 3 of chemotherapy. | Drug: Treatment Crofelemer 125 mg BID during cycles 1-2 of THP or TCHP |
| No Intervention: Control Patients on the control arm will be on the study for cycles 1-3 of THP or TCHP. Patients on the control arm will not receive crofelemer at any time on this study. |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: 1. Willing and able to provide written informed consent; 2. Men and women ≥18 years of age; 3. Pathologically confirmed diagnosis of HER2 positive breast cancer of any stage (previous treatment is allowed without limits on lines of prior therapy); 4. Scheduled to receive at least 3 consecutive cycles of THP or TCHP; 5. Performance status of 0-2 according to the ECOG scale; 6. Negative pregnancy test at time of informed consent for women of childbearing potential; 7. Able to read, understand, follow the study procedure and complete crofelemer, rescue medication, and bowel movement diaries; 8. Patients may enroll simultaneously on this study and other studies, including but not limited to NSABP B52; 9. Patients with brain metastases (including concurrent steroid treatment) are allowed on this study. 10. Left Ventricular Ejection Fraction (LVEF) greater or equal to 50% at baseline as determined by either ECHO or MUGA Exclusion Criteria: 1. Pregnant and/or breastfeeding; 2. Ongoing irritable bowel syndrome (IBS) or colitis (including but not limited to ulcerative colitis, Crohn's disease, microscopic colitis, etc.); 3. Use of investigational drugs within 3 weeks of signing consent or foreseen use during the study; 4. Use of chemotherapy, trastuzumab, or pertuzumab within the past 3 weeks; 5. Use of antibiotics within the past 7 days (up to 2 prophylactic doses of antibiotics for procedures including, but not limited to port placement, is permitted); 6. Any type of ostomy; 7. Total colectomy; 8. Fecal incontinence; 9. Ongoing radiation induced diarrhea or constipation or planned radiotherapy to the abdomen or pelvis while on study; 10. Active systemic infection requiring ongoing intervention, including but not limited to oral and intravenous antibiotics, anti-fungals, anti-parasites, anti-virals; 11. Abdominal or pelvic surgery without recovery of bowel function; 12. Inadequate organ function for starting THP or TCHP, which may include the following laboratory results within 28 days prior to signing consent: 1. Total bilirubin > upper limit of normal (ULN) (unless the patient has documented Gilbert's syndrome) 2. Serum creatinine > 2.0 mg/dL or 177 μmol/L 3. AST (SGOT) and ALT (SPGT) > 2.5 ULN. |
Outcome
Primary Outcome Measures
1. All grade diarrhea [29 months]
Secondary Outcome Measures
1. Diarrhea any grade [29 months]
2. Grade 3-4 diarrhea [29 months]
3. Diarrhea onset [29 months]
4. Diarrhea duration [29 months]
5. Duration grade 3-4 diarrhea [29 months]
6. Anti-diarrheal medications [29 months]
7. FACIT-D total score [29 months]
8. FACIT-D diarrhea score [29 months]
9. Stool frequency and consistency [29 months]
