Clinical trial NCT02910219: Diarrhea Prevention and Prophylaxis With Crofelemer in HER2 Positive Breast Cancer Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: HER2
pertuzumab
trastuzumab
docetaxel
paclitaxel
carboplatin
crofelemer
chemotherapy induced diarrhea
Lead sponsor: Georgetown University
Sponsor class: OTHER
Collaborators: name: Lombardi Comprehensive Cancer Center
name: Medstar Health Research Institute
name: Genentech, Inc.
name: Napo Pharmaceuticals, Inc.
First posted: 2016-09-21
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: Diarrhea for >= 2 Consecutive Days
timeFrame: Cycle 1, Cycle 2 (each cycle is 21 days)
Secondary outcomes:
measure: Diarrhea Any Grade
timeFrame: Cycle 1, Cycle 2 (each cycle is 21 days)
measure: Grade 3-4 Diarrhea
timeFrame: Cycle 1, Cycle 2 (each cycle is 21 days)
measure: Diarrhea Onset
timeFrame: from baseline through Cycle 3 (21 day cycles)
measure: Diarrhea Duration
timeFrame: Cycle 1, Cycle 2 (each cycle is 21 days)
measure: Duration Grade 3-4 Diarrhea
timeFrame: End of Cycle 2 (each cycle is 21 days)
measure: Anti-diarrheal Medications
timeFrame: Cycle 1, Cycle 2 (each cycle is 21 days)
measure: FACIT-D Total Score
timeFrame: Cycle 1, Cycle 2 (each cycle is 21 days)
measure: FACIT-D Diarrhea Score
timeFrame: Cycle 1, Cycle 2 (each cycle is 21 days)
measure: Stool Frequency Based on Consistency (Bristol Stool Scale)
timeFrame: Cycle 1, Cycle 2 (each cycle is 21 days)
Other outcomes:
Locations:
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Baltimore
country: United States
facility: MedStar Franklin Square Cancer Center at Loch Raven Campus
state: Maryland
city: Baltimore
country: United States
facility: Harry and Jeanette Weinberg Cancer Institute
state: Maryland
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack Univ
state: New Jersey
Study officials:
References:
citation: 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.
citation: Pohlmann PR, Graham D, Wu T, Ottaviano Y, Mohebtash M, Kurian S, McNamara D, Lynce F, Warren R, Dilawari A, Rao S, Mainor C, Swanson N, Tan M, Isaacs C, Swain SM. HALT-D: a randomized open-label phase II study of crofelemer for the prevention of chemotherapy-induced diarrhea in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and a taxane. Breast Cancer Res Treat. 2022 Dec;196(3):571-581. doi: 10.1007/s10549-022-06743-9. Epub 2022 Oct 25.