Crofelemer in Preventing Diarrhea in Patients with Her2 Positive Breast Cancer Receiving Trastuzumab, Pertuzumab, and Docetaxel or Paclitaxel with or without Carboplatin

Status: Active

Description

This randomized phase II trial studies how well crofelemer works in preventing diarrhea in patients with Her2 positive breast cancer who are receiving trastuzumab, pertuzumab, and docetaxel or paclitaxel with or without carboplatin. Crofelemer may prevent the movement of chloride in the gut so as to prevent diarrhea.

Eligibility Criteria

Inclusion Criteria

  • Willing and able to provide written informed consent
  • 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 Eastern Cooperative Oncology Group (ECOG) scale
  • Negative pregnancy test at time of signing 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 are allowed on this study (concurrent treatment with steroids is allowed)
  • Left ventricular ejection fraction (LVEF) greater or equal to 50% at baseline as determined by either echocardiogram (ECHO) or multigated acquisition (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 laxatives within the past 7 days
  • Use of chronic laxatives (>= 30 consecutive days)
  • Use of anti-diarrheal agents (including but not limited to loperamide, octreotide, bismuth, tincture of opium, atropine, probiotics in any form other than food) within the past 7 days
  • Use of antibiotics within the past 7 days
  • 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
  • Major abdominal or pelvic surgery within the past 6 months
  • Within 28 days prior to signing consent: Total bilirubin > upper limit of normal (ULN) (unless the patient has documented Gilbert’s syndrome)
  • Within 28 days prior to signing consent: Serum creatinine > 2.0 mg/dL or 177 umol/L
  • Within 28 days prior to signing consent: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT]) > 2.5 ULN

Locations & Contacts

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: Active
Contact: Paula Raffin Pohlmann
Phone: 202-444-2198
Email: paula.r.pohlmann@gunet.georgetown.edu

Maryland

Baltimore
MedStar Franklin Square Medical Center / Weinberg Cancer Institute
Status: Active
Contact: Mahsa Mohebtash
Email: mahsa.mohebtash@medstar.net
MedStar Good Samaritan Hospital
Status: Active
Contact: Mahsa Mohebtash
Email: mahsa.mohebtash@medstar.net

New Jersey

Hackensack
Hackensack University Medical Center
Status: Active
Contact: Deena Mary Atieh Graham
Email: deena.graham@hackensackmeridian.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the efficacy of crofelemer in preventing chemotherapy induced diarrhea (CID) in patients with HER2 positive breast cancer receiving chemotherapy with trastuzumab, pertuzumab, and docetaxel or paclitaxel (THP) or trastuzumab, pertuzumab, carboplatin, and docetaxel (TCHP).

SECONDARY OBJECTIVES:

I. To determine the incidence of diarrhea of any grade, as measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0, by cycle and by stratum.

II. To determine the incidence of diarrhea of grade 3-4, as measured by CTCAE v4.0, by cycle and by stratum.

III. To determine the time to onset of first event of diarrhea of any grade, defined as the number of days from day one of THP or TCHP until the day in which the first episode of diarrhea classified as of grade 1 or higher occurs, or is censored at the date of the last treatment cycle for patients who do not experience diarrhea, overall and by stratum.

IV. To determine the duration (days) of any grade diarrhea, by cycle in which the episode started and by stratum.

V. To determine the duration (days) of grade 3-4 diarrhea, by cycle in which the episode started and by stratum.

VI. To assess use of anti-diarrheal medications (other than study drug), by cycle and grade of diarrhea and by stratum.

VII. To determine the quantitative Functional Assessment of Chronic Illness Therapy-Diarrhea (FACIT-D) total score, collected day 1 of each cycle and at the time of study completion (defined as cycle 4 day 1, but patients may complete this final FACIT-D questionnaire within 5 days of cycle 4 day 1), by cycle and by stratum.

VIII. To determine the quantitative FACIT-D diarrhea subset (DS) score, collected day 1 of each cycle and at the time of study completion (defined as cycle 4 day 1, but patients may complete this final FACIT-D questionnaire within 5 days of cycle 4 day 1), by cycle and by stratum.

IX. To determine the frequency table for stool consistency, as measured by the Bristol Stool scale, by cycle and stratum for each treatment group.

OUTLINE: Patients are randomized into 1 of 2 groups.

GROUP I: Patients receive crofelemer orally (PO) twice daily (BID) during courses 1-2 (21 days per course) of THP or TCHP chemotherapy in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive standard of care during THP or TCHP chemotherapy.

After completion of study, patients are followed up until course 4 day 1 of THP or TCHP or until 30 days after last dose of crofelemer, whichever occurs later.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Prevention

Lead Organization

Lead Organization
MedStar Georgetown University Hospital

Principal Investigator
Paula Raffin Pohlmann

Trial IDs

Primary ID 2015-0547
Secondary IDs NCI-2017-02455
Clinicaltrials.gov ID NCT02910219