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

October 20, 2022 updated by: Sandra Swain

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Lombardi Comprehensive Cancer Center
    • Maryland
      • Baltimore, Maryland, United States, 21218
        • Medstar Franklin Square Cancer Center at Loch Raven Campus
      • Baltimore, Maryland, United States, 21237
        • Harry and Jeanette Weinberg Cancer Institute
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center at Hackensack Univ

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Crofelemer
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diarrhea for >= 2 Consecutive Days
Time Frame: Cycle 1, Cycle 2 (each cycle is 21 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diarrhea Any Grade
Time Frame: Cycle 1, Cycle 2 (each cycle is 21 days)
Incidence of diarrhea of any grade, as measured by CTCAE v4.0, by cycle
Cycle 1, Cycle 2 (each cycle is 21 days)
Grade 3-4 Diarrhea
Time Frame: Cycle 1, Cycle 2 (each cycle is 21 days)
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)
Diarrhea Onset
Time Frame: from baseline through Cycle 3 (21 day cycles)
Time to onset of first episode of diarrhea of any grade, overall
from baseline through Cycle 3 (21 day cycles)
Diarrhea Duration
Time Frame: Cycle 1, Cycle 2 (each cycle is 21 days)
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)
Duration Grade 3-4 Diarrhea
Time Frame: End of Cycle 2 (each cycle is 21 days)
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)
Anti-diarrheal Medications
Time Frame: Cycle 1, Cycle 2 (each cycle is 21 days)
Use of anti-diarrheal medications (other than study drug), by cycle and arm
Cycle 1, Cycle 2 (each cycle is 21 days)
FACIT-D Total Score
Time Frame: Cycle 1, Cycle 2 (each cycle is 21 days)
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)
FACIT-D Diarrhea Score
Time Frame: Cycle 1, Cycle 2 (each cycle is 21 days)
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)
Stool Frequency Based on Consistency (Bristol Stool Scale)
Time Frame: Cycle 1, Cycle 2 (each cycle is 21 days)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sandra Swain

Collaborators

Genentech, Inc.
Medstar Health Research Institute
Lombardi Comprehensive Cancer Center
Napo Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 31, 2017

Primary Completion (Actual)

November 23, 2020

Study Completion (Actual)

November 23, 2020

Study Registration Dates

First Submitted

September 19, 2016

First Submitted That Met QC Criteria

September 19, 2016

First Posted (Estimate)

September 21, 2016

Study Record Updates

Last Update Posted (Actual)

October 24, 2022

Last Update Submitted That Met QC Criteria

October 20, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MHRI GU 2015-0547

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

No plan to make individual participant data available

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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