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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California
study started
estimated completion:

Description

Summary

This is a study to evaluate the toxicity profile of neratinib in combination with trastuzumab in patients with early stage breast cancer with the use of anti-diarrheal prophylaxis. The anti-diarrheal medications being tested in this trial are loperamide and crofelemer. Crofelemer is an anti-diarrheal, enteric-coated drug product for oral administration. It is the only botanical drug currently approved by the FDA for oral administration and is approved for the treatment of diarrhea associated with HAART. Crofelemer has a novel mechanism of action, acting directly and simultaneously on 2 distinct intestinal luminal chloride channels. It is an inhibitor of both the cyclic adenosine monophosphate (cAMP)-stimulated cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion (Cl-) channel found on the apical membranes, and the calcium-activated Cl- channels (CaCC) at the luminal membrane of enterocytes. The CFTR Cl-channel and CaCC regulate Cl and fluid secretion by intestinal epithelial cells. Crofelemer acts by blocking Cl- secretion and accompanying high volume water loss in diarrhea, normalizing the flow of Cl- and water in the GI tract.

Official Title

An Open Label Study to Characterize the Incidence and Severity of Diarrhea in Patients With Early Stage HER2+ Breast Cancer Treated With Adjuvant Trastuzumab and Neratinib Followed by Neratinib Monotherapy, and Intensive Anti-diarrhea Prophylaxis

Details

This is an open-label adjuvant/post neoadjuvant single arm phase 2 trial.

Patients will receive:

Neratinib 240 mg orally once a day for up to 52 weeks while receiving concurrent trastuzumab. After the completion of trastuzumab maintenance therapy (determined by treating physician), neratinib will continue as monotherapy for 12 months. Neratinib is to be taken continuously in 21-day cycles with no rest between cycles unless related to toxicity.

Intensive daily loperamide prophylaxis for the first 2 cycles and then as needed.

Crofelemer 125 mg bid for the first two cycles then as needed.

Each cycle is 21 days. Clinic visits and laboratory studies are planned on day 1 of every cycle for the first 4 cycles, then q4 cycles thereafter. An end of treatment visit will occur 28 days after the last dose of neratinib. Patients who permanently discontinue treatment due to unacceptable toxicity will be followed-up for 28 days after the last dose of neratinib.

Keywords

HER2-positive Breast Cancer neratinib trastuzumab crofelemer Breast Neoplasms Diarrhea Loperamide Antidiarrheals

Eligibility

You can join if…

Open to people ages 18 years and up

A patient will be eligible for this study if she/he meets any of the following criteria.

  1. Aged ≥18 years at signing of informed consent.
  2. Histologically confirmed clinical or pathological stage 2 through stage 3c primary adenocarcinoma of the breast.
  3. Documented HER2 overexpression or gene-amplified tumor by a validated approved method.
  4. Patients can have HR+ or HR-negative disease.
  5. Concurrent adjuvant endocrine therapy and bone-modifying agents is allowed
  6. Patients can be premenopausal or postmenopausal
  7. Completion of neoadjuvant or adjuvant chemotherapy
  8. Completion of adjuvant locoregional radiation, if indicated, is required prior to starting study treatment.
  9. At the time of study enrollment, patients must have at least 4 months of adjuvant trastuzumab planned
  10. . Clinically no evidence of local, regional, or metastatic disease at the time of study entry
  11. . Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
  12. . Eastern Cooperative Oncology Group (ECOG) status of 0 to 1.
  13. . Negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause. [Women are considered postmenopausal if they are ≥12 months without menses, in the absence of endocrine or anti-endocrine therapies].
  14. . Trastuzumab can cause embryo-fetal harm when administered during pregnancy and the effects of neratinib on the developing human fetus are unknown. Women of child-bearing potential must agree and commit to use of a highly effective double-barrier method of contraception (e.g., a combination of male condom with an intravaginal device such as the cervical cap, diaphragm, or vaginal sponge with spermicide) or a non-hormonal method, from the signing of informed consent until 28 days after the last dose of neratinib and 7 months after the last dose of trastuzumab, or consent to total sexual abstinence (abstinence must occur from randomization and continue for 28 days after the last dose of neratinib and 7 months after the last dose of trastuzumab). Men without confirmed vasectomy must agree and commit to use a barrier method of contraception while on treatment and for 3 months after the last dose of investigational products, or consent to total sexual abstinence (abstinence must occur from randomization and continue for 3 months after the last dose of study medication).
  15. . Recovery (i.e., to Grade 1 or baseline) from all clinically significant AEs related to prior therapies (excluding alopecia, neuropathy, and nail changes).
  16. . Provide written, informed consent to participate in the study and follow the study procedures.

You CAN'T join if...

A patient will be excluded from this study if she/he meets any of the following criteria.

  1. Clinical or radiologic evidence of local or regional recurrence of disease or metastatic disease prior to or at the time of study entry.
  2. Currently receiving chemotherapy, radiation therapy, investigational immunotherapy, or investigational biotherapy for breast cancer.
  3. Major surgery (including breast surgery) within <30 days of starting treatment or received chemotherapy, investigational agents, or other cancer therapy <14 days prior to the initiation of investigational products (except adjuvant endocrine therapy).
  4. Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2; including individuals who currently use digitalis, beta-blockers, or calcium channel blockers specifically for congestive heart failure), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia.
  5. QTc interval >0.450 seconds (males) or >0.470 seconds (females), or known history of QTc prolongation or Torsade de Pointes (TdP).
  6. Screening laboratory assessments outside the following limits:

Absolute neutrophil count (ANC): ≤1,000 /μL Platelets: ≤100,000 /μL Hemoglobin: ≤9 g/dL Serum creatinine or calculated creatinine clearance†: ≥1.5 x upper limit of normal (ULN) OR ≤30 mL/min for patients with creatinine levels >1.5 x institutional

ULN Serum total bilirubin: ≥1.5 x ULN OR direct bilirubin ≥ ULN for patients with total bilirubin levels >1.5 x ULN AST (SGOT) and ALT (SGPT): ≥2.5 x ULN

† Creatinine clearance should be calculated per institutional standard.

  1. Patients with a second malignancy, other than adequately treated non-melanoma skin cancers, in situ melanoma or in situ cervical cancer. Patients with other non-mammary malignancies must have been disease-free for at least 5 years.
  2. Currently pregnant or breast-feeding.
  3. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g.,Crohn's disease, malabsorption, or Grade ≥2 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 4.0 [CTCAE v.4.0] diarrhea of any etiology at baseline).
  4. . Clinically active infection with hepatitis B or hepatitis C virus.
  5. . Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that could, in the Investigator's judgment, make the patient inappropriate for this study.
  6. . Known hypersensitivity to any component of the investigational products.
  7. . Unable or unwilling to swallow tablets.

Location

  • UCSF Helen Diller Family Comprehensive Cancer Center accepting new patients
    San Francisco, California, 94115, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT03094052
Phase
Phase 2
Lead Scientist
Jo Chien
Study Type
Interventional
Last Updated
August 30, 2017
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