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

Primary Purpose

Breast Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Crofelemer

About this trial

This is an interventional prevention trial for Breast Cancer focused on measuring HER2, pertuzumab, trastuzumab, docetaxel, paclitaxel, carboplatin, crofelemer, chemotherapy induced diarrhea

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Willing and able to provide written informed consent;
Men and women ≥18 years of age;
Pathologically confirmed diagnosis of HER2 positive breast cancer of any stage (previous treatment is allowed without limits on lines of prior therapy);
Scheduled to receive at least 3 consecutive cycles of THP or TCHP;
Performance status of 0-2 according to the ECOG scale;
Negative pregnancy test at time of informed consent for women of childbearing potential;
Able to read, understand, follow the study procedure and complete crofelemer, rescue medication, and bowel movement diaries;
Patients may enroll simultaneously on this study and other studies, including but not limited to NSABP B52;
Patients with brain metastases (including concurrent steroid treatment) are allowed on this study.
Left Ventricular Ejection Fraction (LVEF) greater or equal to 50% at baseline as determined by either ECHO or MUGA

Exclusion Criteria:

Pregnant and/or breastfeeding;
Ongoing irritable bowel syndrome (IBS) or colitis (including but not limited to ulcerative colitis, Crohn's disease, microscopic colitis, etc.);
Use of investigational drugs within 3 weeks of signing consent or foreseen use during the study;
Use of chemotherapy, trastuzumab, or pertuzumab within the past 3 weeks;
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);
Any type of ostomy;
Total colectomy;
Fecal incontinence;
Ongoing radiation induced diarrhea or constipation or planned radiotherapy to the abdomen or pelvis while on study;
Active systemic infection requiring ongoing intervention, including but not limited to oral and intravenous antibiotics, anti-fungals, anti-parasites, anti-virals;
Abdominal or pelvic surgery without recovery of bowel function;
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.

Sites / Locations

Lombardi Comprehensive Cancer Center
MedStar Franklin Square Cancer Center at Loch Raven Campus
Harry and Jeanette Weinberg Cancer Institute
John Theurer Cancer Center at Hackensack Univ

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Crofelemer

Control

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Diarrhea Any Grade

Incidence of diarrhea of any grade, as measured by CTCAE v4.0, by cycle

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

Diarrhea Onset

Time to onset of first episode of diarrhea of any grade, overall

Diarrhea Duration

Duration (days) of any grade diarrhea, defined from day 1 to day 21, by cycle in which the episode started

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

Anti-diarrheal Medications

Use of anti-diarrheal medications (other than study drug), by cycle and arm

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.

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.

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).

Full Information

NCT ID

NCT02910219

First Posted

September 19, 2016

Last Updated

October 20, 2022

Sponsor

Sandra Swain

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT02910219

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Completed

Study Start Date

January 31, 2017 (Actual)

Primary Completion Date

November 23, 2020 (Actual)

Study Completion Date

November 23, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Sandra Swain

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

HER2, pertuzumab, trastuzumab, docetaxel, paclitaxel, carboplatin, crofelemer, chemotherapy induced diarrhea

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

53 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Crofelemer

Arm Type

Experimental

Arm Description

Arm Title

Control

Arm Type

No Intervention

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Crofelemer

Intervention Description

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

Primary Outcome Measure Information:

Title

Diarrhea for >= 2 Consecutive Days

Description

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.

Time Frame

Cycle 1, Cycle 2 (each cycle is 21 days)

Secondary Outcome Measure Information:

Title

Diarrhea Any Grade

Description

Incidence of diarrhea of any grade, as measured by CTCAE v4.0, by cycle

Time Frame

Cycle 1, Cycle 2 (each cycle is 21 days)

Title

Grade 3-4 Diarrhea

Description

number of patients with diarrhea of grade 3 or grade 4, as measured by CTCAE v4.0, by cycle and by stratum

Time Frame

Cycle 1, Cycle 2 (each cycle is 21 days)

Title

Diarrhea Onset

Description

Time to onset of first episode of diarrhea of any grade, overall

Time Frame

from baseline through Cycle 3 (21 day cycles)

Title

Diarrhea Duration

Description

Duration (days) of any grade diarrhea, defined from day 1 to day 21, by cycle in which the episode started

Time Frame

Cycle 1, Cycle 2 (each cycle is 21 days)

Title

Duration Grade 3-4 Diarrhea

Description

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

Time Frame

End of Cycle 2 (each cycle is 21 days)

Title

Anti-diarrheal Medications

Description

Use of anti-diarrheal medications (other than study drug), by cycle and arm

Time Frame

Cycle 1, Cycle 2 (each cycle is 21 days)

Title

FACIT-D Total Score

Description

Time Frame

Cycle 1, Cycle 2 (each cycle is 21 days)

Title

FACIT-D Diarrhea Score

Description

Time Frame

Cycle 1, Cycle 2 (each cycle is 21 days)

Title

Stool Frequency Based on Consistency (Bristol Stool Scale)

Description

Time Frame

Cycle 1, Cycle 2 (each cycle is 21 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Willing and able to provide written informed consent; Men and women ≥18 years of age; Pathologically confirmed diagnosis of HER2 positive breast cancer of any stage (previous treatment is allowed without limits on lines of prior therapy); Scheduled to receive at least 3 consecutive cycles of THP or TCHP; Performance status of 0-2 according to the ECOG scale; Negative pregnancy test at time of informed consent for women of childbearing potential; Able to read, understand, follow the study procedure and complete crofelemer, rescue medication, and bowel movement diaries; Patients may enroll simultaneously on this study and other studies, including but not limited to NSABP B52; Patients with brain metastases (including concurrent steroid treatment) are allowed on this study. Left Ventricular Ejection Fraction (LVEF) greater or equal to 50% at baseline as determined by either ECHO or MUGA Exclusion Criteria: Pregnant and/or breastfeeding; Ongoing irritable bowel syndrome (IBS) or colitis (including but not limited to ulcerative colitis, Crohn's disease, microscopic colitis, etc.); Use of investigational drugs within 3 weeks of signing consent or foreseen use during the study; Use of chemotherapy, trastuzumab, or pertuzumab within the past 3 weeks; 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); Any type of ostomy; Total colectomy; Fecal incontinence; Ongoing radiation induced diarrhea or constipation or planned radiotherapy to the abdomen or pelvis while on study; Active systemic infection requiring ongoing intervention, including but not limited to oral and intravenous antibiotics, anti-fungals, anti-parasites, anti-virals; Abdominal or pelvic surgery without recovery of bowel function; Inadequate organ function for starting THP or TCHP, which may include the following laboratory results within 28 days prior to signing consent: Total bilirubin > upper limit of normal (ULN) (unless the patient has documented Gilbert's syndrome) Serum creatinine > 2.0 mg/dL or 177 μmol/L AST (SGOT) and ALT (SPGT) > 2.5 ULN.

Facility Information:

Facility Name

Lombardi Comprehensive Cancer Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

MedStar Franklin Square Cancer Center at Loch Raven Campus

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21218

Country

United States

Facility Name

Harry and Jeanette Weinberg Cancer Institute

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21237

Country

United States

Facility Name

John Theurer Cancer Center at Hackensack Univ

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

No plan to make individual participant data available

Citations:

PubMed Identifier

27692565

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.

Results Reference

background

PubMed Identifier

36280642

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.

Results Reference

derived

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

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