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Diarrhea Prevention and Prophylaxis With Crofelemer in HER2 Positive Breast Cancer Patients (HALT-D)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02910219
Recruitment Status : Recruiting
First Posted : September 21, 2016
Last Update Posted : June 12, 2018
Lombardi Comprehensive Cancer Center
Medstar Health Research Institute
Genentech, Inc.
Napo Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Paula R. Pohlmann, MD, PhD, Georgetown University

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Crofelemer Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : January 31, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Crofelemer

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: Crofelemer
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.

Primary Outcome Measures :
  1. All grade diarrhea [ Time Frame: 29 months ]
    Incidence of all grade diarrhea lasting 2 or more consecutive days during cycles 1 and 2 of chemotherapy

Secondary Outcome Measures :
  1. Diarrhea any grade [ Time Frame: 29 months ]
    Incidence of diarrhea of any grade, as measured by CTCAE v4.0, by cycle and by stratum

  2. Grade 3-4 diarrhea [ Time Frame: 29 months ]
    Incidence of diarrhea of grade 3-4, as measured by CTCAE v4.0, by cycle and by stratum

  3. Diarrhea onset [ Time Frame: 29 months ]
    Time to onset of first episode of diarrhea of any grade, overall and by stratum

  4. Diarrhea duration [ Time Frame: 29 months ]
    Duration (days) of any grade diarrhea, defined from day 1 to day 21, by cycle in which the episode started and by stratum

  5. Duration grade 3-4 diarrhea [ Time Frame: 29 months ]
    Duration (days) of grade 3-4 diarrhea, defined from day 1 to day 21, by cycle in which the episode started and by stratum

  6. Anti-diarrheal medications [ Time Frame: 29 months ]
    Use of anti-diarrheal medications (other than study drug), by cycle and grade

  7. FACIT-D total score [ Time Frame: 29 months ]
    Quantitative FACIT-D total score, collected day 1 of each cycle and at the time of study completion, by cycle and by stratum

  8. FACIT-D diarrhea score [ Time Frame: 29 months ]
    Quantitative FACIT-D diarrhea subset (DS) score, by cycle and by stratum

  9. Stool frequency and consistency [ Time Frame: 29 months ]
    Frequency table of stool consistency, as measured by the Bristol Stool scale, by cycle stratum between treatment groups

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02910219

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Contact: Paula R Pohlmann, MD, PhD 202-444-2198
Contact: Antonella Novielli, RN, MSN 202-784-3923

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United States, District of Columbia
Lombardi Comprehensive Cancer Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Ann Gallagher, MS    202 687-3981   
Contact: Julie Castle, RN, BSN, OCN    202-687-2209   
Principal Investigator: Sandra M Swain, MD, FACP, FASCO         
Principal Investigator: Paula R Pohlmann, MD, PhD         
Sub-Investigator: Jennifer J Gao, MD         
United States, Maryland
MedStar Franklin Square Cancer Center at Loch Raven Campus Recruiting
Baltimore, Maryland, United States, 21218
Contact: Barbara Rector, RN    410-261-8151   
Principal Investigator: Mahsa Mohebtash, MD         
Harry and Jeanette Weinberg Cancer Institute Recruiting
Baltimore, Maryland, United States, 21237
Contact: Yvonne Ottaviano, MD    443-777-7147      
Principal Investigator: Yvonne Ottaviano, MD         
United States, New Jersey
John Theurer Cancer Center at Hackensack Univ Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Deena Graham, MD    551-996-5811      
Sponsors and Collaborators
Georgetown University
Lombardi Comprehensive Cancer Center
Medstar Health Research Institute
Genentech, Inc.
Napo Pharmaceuticals, Inc.

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Paula R. Pohlmann, MD, PhD, Medical Oncologist, Georgetown University Identifier: NCT02910219    
Other Study ID Numbers: MHRI GU 2015-0547
First Posted: September 21, 2016    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to make individual participant data available

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Paula R. Pohlmann, MD, PhD, Georgetown University:
chemotherapy induced diarrhea
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological