Summary

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

Description

Summary

An Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients with Early-Stage HER2+ Breast Cancer Treated with Neratinib and Intensive Loperamide Prophylaxis

Official Title

An Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients With Early-Stage HER2+ Breast Cancer Treated With Neratinib and Intensive Loperamide Prophylaxis

Details

This is an open-label, Phase 2 study that will investigate the incidence and severity of diarrhea in early-stage HER2+ breast cancer patients receiving neratinib with intensive loperamide diarrhea prophylaxis, alone and in combination with an anti-inflammatory treatment or a bile acid sequestrant treatment, who have previously undergone a course of trastuzumab therapy in the adjuvant setting.

Patients will receive:

  • Neratinib 240 mg orally once daily with food for thirteen (13) 28-day cycles.
  • Loperamide daily for two (2) 28-day cycles and then as needed.
  • For patients enrolled under Amendment 3, an anti-inflammatory treatment for 1 cycle and loperamide to be administered daily for two (2) 28-day cycles and then as needed, thereafter;
  • For patients enrolled under Amendment 4, colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter;
  • For patients enrolled under Amendment 5, colestipol for 1 cycle and loperamide to be administered on an as-needed basis only.
  • For patients enrolled under Amendment 6, 120 mg neratinib for Week 1, followed by 160 mg neratinib starting for Week 2, followed by 240 mg neratinib starting at Week 3 and thereafter. Loperamide will be administered on an as-needed basis only.

Keywords

Early Stage HER2+ Breast Cancer HER2 + Breast Cancer Neratinib Nerlynx Loperamide Colestipol Budesonide Breast Neoplasms Diarrhea Antidiarrheals Budesonide and Loperamide Colestipol and Loperamide Neratinib dose escalation

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Aged ≥18 years at signing of informed consent
  2. Histologically confirmed stage 1 through stage 3c primary adenocarcinoma of the breast
  3. Documented HER2 overexpression or gene-amplified tumor by a validated approved method
  4. Patients must have completed a course of prior adjuvant trastuzumab or experienced side effects that resulted in early discontinuation of trastuzumab that have since resolved
  5. The last dose of trastuzumab must have been given >2 weeks and ≤1 year (365 days) from enrollment
  6. Physician assessment confirming that the patient is negative for local or regional recurrence of disease or metastatic disease at the time of study entry, including:
  7. Per standard of care, bone scan or positron emission tomography (PET) scan;required only if alkaline phosphatase (ALP) is ≥2 x upper limit of normal (ULN)and/or there are symptoms of metastatic bone disease. A confirmatory imaging study is required if the results from the bone scan are questionable.
  8. Per standard of care, computed tomography (CT), magnetic resonance imaging (MRI)or ultrasound of the abdomen and chest; required only if aspartate aminotransferase (AST)/alanine aminotransferase (ALT) or ALP is ≥2 x ULN.
  9. Other radiologic assessments may be performed to rule out underlying breast cancer recurrence if indicated and as per standard of care (for patients enrolled starting with Amendment 6.1).
  10. Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO)
  11. Eastern Cooperative Oncology Group (ECOG) status of 0 to 1
  12. 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.]
  13. . Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception, ie, intrauterine device, bilateral tubal ligation, vasectomized partner, or abstinence (only when it is the preferred lifestyle of the patient), from the time of informed consent until 28 days after the last dose of the investigational products. Man (male patient) with female partner of childbearing potential must agree and commit to use condom and the female partner must agree and commit to use a highly effective method of contraception (ie, any of the above methods, or for females, hormonal contraception associated with inhibition of ovulation) while on treatment and for 3 months after last dose of investigational products.
  14. . Recovery (ie, to Grade 1 or baseline) from all clinically significant AEs related to prior therapies (excluding alopecia, neuropathy, and nail changes)
  15. . Provide written, informed consent to participate in the study and follow the study procedures

You CAN'T join if...

  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, immunotherapy, or biotherapy for breast cancer
  3. Major surgery within <30 days of starting treatment or received chemotherapy,investigational agents, or other cancer therapy, except hormonal therapy (eg,tamoxifen, aromatase inhibitors), <14 days prior to the initiation of investigational products
  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 (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 (<1.0 x 109/L); Platelet count <100,000/μl(<100 x 109/L); Hemoglobin <9 g/dL; Total bilirubin >1.5 x institutional upper limit of normal (ULN) (i n case of known Gilbert's syndrome, <2 x ULN is allowed); Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x institutional ULN;Creatinine Creatinine clearance <30 mL/min (as calculated by Cockcroft-Gault formula or Modification of Diet in Renal Disease [MDRD] formula)

  1. Active, unresolved infections
  2. 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 5years
  3. Currently pregnant or breast-feeding
  4. . Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg,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)
  5. . Clinically active infection with hepatitis B or hepatitis C virus
  6. . 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
  7. . Known hypersensitivity to any component of the investigational products; known hypersensitivity to salicylates; known hypersensitivity to aspartame-containing products for patients with phenylketonuria; known allergies to any of the medications or components of medications used in the trial
  8. . Unable or unwilling to swallow tablets

Locations

  • UCSF Helen Diller Family Comprehensive Cancer Center accepting new patients
    San Francisco California 94115 United States
  • St. Jude Hospital Yorba Linda DBA Saint Joseph Heritage Healthcare withdrawn
    Santa Rosa California 95403 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Puma Biotechnology, Inc.
ID
NCT02400476
Phase
Phase 2
Lead Scientist
Amy Chien
Study Type
Interventional
Last Updated
August 17, 2018