Diarrhea Prevention and Prophylaxis With Crofelemer in HER2 Positive Breast Cancer Patients

Breast Cancer Clinical Trial

— HALT-D  

Official title:

Diarrhea Prevention and Prophylaxis With Crofelemer in HER2 Positive Breast Cancer Patients Receiving Trastuzumab, Pertuzumab, and Docetaxel or Paclitaxel With or Without Carboplatin: HALT-D

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02910219
• Other study ID #: MHRI GU 2015-0547
• Status: Completed
• Phase: Phase 2
• Start date: January 31, 2017
• Est. completion date: November 23, 2020

Study information

• Verified date: October 2022
• Source: Georgetown University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Chemotherapy induced diarrhea is seen in up to 40-80% of patients receiving this treatment for HER2 positive locally advanced or metastatic breast cancer. This diarrhea can significantly impact a patient's quality of life and ability to tolerate chemo/anti-HER2 therapy. This study will look at the efficacy of the drug crofelemer in preventing diarrhea in breast cancer patients.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: November 23, 2020
• Est. primary completion date: November 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Diarrhea

Intervention

Drug:
• Crofelemer
Crofelemer 125 mg BID during cycles 1-2 of THP or TCHP

Locations

Country	Name	City	State
United States	Harry and Jeanette Weinberg Cancer Institute	Baltimore	Maryland
United States	MedStar Franklin Square Cancer Center at Loch Raven Campus	Baltimore	Maryland
United States	John Theurer Cancer Center at Hackensack Univ	Hackensack	New Jersey
United States	Lombardi Comprehensive Cancer Center	Washington	District of Columbia

Sponsors (5)

Lead Sponsor	Collaborator
Sandra Swain	Genentech, Inc., Lombardi Comprehensive Cancer Center, Medstar Health Research Institute, Napo Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Gao JJ, Tan M, Pohlmann PR, Swain SM. HALT-D: A Phase II Evaluation of Crofelemer for the Prevention and Prophylaxis of Diarrhea in Patients With Breast Cancer on Pertuzumab-Based Regimens. Clin Breast Cancer. 2017 Feb;17(1):76-78. doi: 10.1016/j.clbc.2016.08.005. Epub 2016 Aug 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diarrhea for >= 2 Consecutive Days	Percentage of participants with any grade (based on CTCAE 4.0) diarrhea lasting 2 or more consecutive days during cycles 1 and 2 of chemotherapy.	Cycle 1, Cycle 2 (each cycle is 21 days)
Secondary	Diarrhea Any Grade	Incidence of diarrhea of any grade, as measured by CTCAE v4.0, by cycle	Cycle 1, Cycle 2 (each cycle is 21 days)
Secondary	Grade 3-4 Diarrhea	number of patients with diarrhea of grade 3 or grade 4, as measured by CTCAE v4.0, by cycle and by stratum	Cycle 1, Cycle 2 (each cycle is 21 days)
Secondary	Diarrhea Onset	Time to onset of first episode of diarrhea of any grade, overall	from baseline through Cycle 3 (21 day cycles)
Secondary	Diarrhea Duration	Duration (days) of any grade diarrhea, defined from day 1 to day 21, by cycle in which the episode started	Cycle 1, Cycle 2 (each cycle is 21 days)
Secondary	Duration Grade 3-4 Diarrhea	Duration (days) of grade 3-4 diarrhea during cycle 1 through the end of cycle 2, defined from cycle day 1 to cycle 2 day 21	End of Cycle 2 (each cycle is 21 days)
Secondary	Anti-diarrheal Medications	Use of anti-diarrheal medications (other than study drug), by cycle and arm	Cycle 1, Cycle 2 (each cycle is 21 days)
Secondary	FACIT-D Total Score	Quantitative FACIT-D (FACIT-D Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea) total score, collected day 1 of each cycle and at the time of study completion, cycles 1 and 2 reported; The higher the score the better the QOL; Score range 0-152.	Cycle 1, Cycle 2 (each cycle is 21 days)
Secondary	FACIT-D Diarrhea Score	Quantitative FACIT-D (FACIT-D Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea) diarrhea subscale (DS) score, by cycle; Score Range 0-44; the higher the score, the better the QOL.	Cycle 1, Cycle 2 (each cycle is 21 days)
Secondary	Stool Frequency Based on Consistency (Bristol Stool Scale)	Frequency of stool consistency of 6-7, as measured by the Bristol Stool scale (minimum 1-separate hard lumps, maximum 7-watery, no solid pieces), by cycle; Median in watery bowel movements (Bristol Stool Form Scale 6-7).	Cycle 1, Cycle 2 (each cycle is 21 days)