HALT-D: A Phase II Evaluation of Crofelemer for the Prevention and Prophylaxis of Diarrhea in Patients With Breast Cancer on Pertuzumab-Based Regimens.
HALT-D: A Phase II Evaluation of Crofelemer for the Prevention and Prophylaxis of Diarrhea in Patients With Breast Cancer on Pertuzumab-Based Regimens.
- 2017
Approximately 40% to 80% of patients receiving pertuzumab-directed therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer will develop chemotherapy-induced diarrhea (CID). Loperamide and octreotide are frequently used to treat CID after diarrhea occurs, but neither is used prophylactically or targets the underlying mechanism. Previous studies suggest blocking epidermal growth factor receptor may cause excess chloride secretion, resulting in diarrhea. Crofelemer is derived from the red latex of the Croton lechleri tree, blocks gastrointestinal cystic fibrosis transmembrane regulator and calcium-activated chloride channels, and is U.S. Food and Drug Administration approved for relief of diarrhea in HIV/AIDS patients on anti-retroviral therapy. Crofelemer is not systemically absorbed, has relatively few side effects, and presents a targeted approach at preventing CID in patients receiving pertuzumab-based therapy. HALT-D (DiarrHeA Prevention and ProphyLaxis with Crofelemer in HER2-Positive Breast Cancer Patients Receiving Trastuzumab, Pertuzumab, and Docetaxel or Paclitaxel with or without Carboplatin, NCT02910219) is a phase II, randomized, open-label trial that aims to recruit 46 patients from 3 MedStar sites. Adults with HER2-positive breast cancer being treated with trastuzumab, pertuzumab, and docetaxel or paclitaxel (THP) or trastuzumab, pertuzumab, docetaxel, and carboplatin (TCHP) will be randomized to receive crofelemer or no medication for diarrhea prophylaxis. The primary endpoint is incidence of all grade diarrhea for > 2 consecutive days during cycles 1 to 2 of THP or TCHP. Secondary endpoints include overall incidence, duration, and severity of diarrhea; time to onset of diarrhea; use of other anti-diarrheal medications; stool frequency and consistency; and quality of life. HALT-D will provide important information about the feasibility and tolerability of crofelemer in preventing diarrhea for patients receiving THP or TCHP. Copyright c 2016 Elsevier Inc. All rights reserved.
English
1526-8209
*Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
*Breast Neoplasms/dt [Drug Therapy]
*Diarrhea/pc [Prevention & Control]
*Proanthocyanidins/tu [Therapeutic Use]
*Quality of Life
Adolescent
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized/ad [Administration & Dosage]
Breast Neoplasms/pa [Pathology]
Carboplatin/ad [Administration & Dosage]
Diarrhea/ci [Chemically Induced]
Diarrhea/ep [Epidemiology]
Female
Follow-Up Studies
Humans
Middle Aged
Neoplasm Staging
Paclitaxel/ad [Administration & Dosage]
Prognosis
Taxoids/ad [Administration & Dosage]
Trastuzumab/ad [Administration & Dosage]
Young Adult
Washington Cancer Institute
Journal Article
Approximately 40% to 80% of patients receiving pertuzumab-directed therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer will develop chemotherapy-induced diarrhea (CID). Loperamide and octreotide are frequently used to treat CID after diarrhea occurs, but neither is used prophylactically or targets the underlying mechanism. Previous studies suggest blocking epidermal growth factor receptor may cause excess chloride secretion, resulting in diarrhea. Crofelemer is derived from the red latex of the Croton lechleri tree, blocks gastrointestinal cystic fibrosis transmembrane regulator and calcium-activated chloride channels, and is U.S. Food and Drug Administration approved for relief of diarrhea in HIV/AIDS patients on anti-retroviral therapy. Crofelemer is not systemically absorbed, has relatively few side effects, and presents a targeted approach at preventing CID in patients receiving pertuzumab-based therapy. HALT-D (DiarrHeA Prevention and ProphyLaxis with Crofelemer in HER2-Positive Breast Cancer Patients Receiving Trastuzumab, Pertuzumab, and Docetaxel or Paclitaxel with or without Carboplatin, NCT02910219) is a phase II, randomized, open-label trial that aims to recruit 46 patients from 3 MedStar sites. Adults with HER2-positive breast cancer being treated with trastuzumab, pertuzumab, and docetaxel or paclitaxel (THP) or trastuzumab, pertuzumab, docetaxel, and carboplatin (TCHP) will be randomized to receive crofelemer or no medication for diarrhea prophylaxis. The primary endpoint is incidence of all grade diarrhea for > 2 consecutive days during cycles 1 to 2 of THP or TCHP. Secondary endpoints include overall incidence, duration, and severity of diarrhea; time to onset of diarrhea; use of other anti-diarrheal medications; stool frequency and consistency; and quality of life. HALT-D will provide important information about the feasibility and tolerability of crofelemer in preventing diarrhea for patients receiving THP or TCHP. Copyright c 2016 Elsevier Inc. All rights reserved.
English
1526-8209
*Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
*Breast Neoplasms/dt [Drug Therapy]
*Diarrhea/pc [Prevention & Control]
*Proanthocyanidins/tu [Therapeutic Use]
*Quality of Life
Adolescent
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized/ad [Administration & Dosage]
Breast Neoplasms/pa [Pathology]
Carboplatin/ad [Administration & Dosage]
Diarrhea/ci [Chemically Induced]
Diarrhea/ep [Epidemiology]
Female
Follow-Up Studies
Humans
Middle Aged
Neoplasm Staging
Paclitaxel/ad [Administration & Dosage]
Prognosis
Taxoids/ad [Administration & Dosage]
Trastuzumab/ad [Administration & Dosage]
Young Adult
Washington Cancer Institute
Journal Article