This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback
Trial record 1 of 1 for:    NCT02400476
Previous Study | Return to List | Next Study

A Study Looking the Incidence and Severity of Diarrhea in Patients With Early-Stage HER2+ Breast Cancer Treated With Neratinib and Loperamide

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Puma Biotechnology, Inc.
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT02400476
First received: February 17, 2015
Last updated: June 19, 2017
Last verified: June 2017
  Purpose
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

Condition Intervention Phase
Early Stage HER2+ Breast Cancer Drug: Neratinib Drug: Loperamide Drug: Budesonide Drug: Colestipol Drug: Bismuth Subsalicylate or Mesalamine Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Puma Biotechnology, Inc.:

Primary Outcome Measures:
  • Incidence of Grade 3 or higher diarrhea [ Time Frame: Length of study (15 months) ]
    The primary objective of this study is to characterize the incidence and severity of diarrhea in patients with early-stage HER2 overexpressed/amplified (HER2+) breast cancer treated with neratinib when administered with intensive loperamide prophylaxis, after prior treatment with trastuzumab.


Secondary Outcome Measures:
  • Incidence and severity of diarrhea by loperamide exposure [ Time Frame: Length of study (15 months) ]
    Evaluate the association between loperamide exposure and the incidence and severity of diarrhea, with and without anti -inflammatory agents; with and without a bile acid sequestrant

  • Incidence of serious adverse events and other adverse events of special interest [ Time Frame: Length of study (15 months) ]
    Assess the incidence of serious adverse events (SAEs) and other adverse events of special interest (AESI)


Estimated Enrollment: 240
Actual Study Start Date: February 2015
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: neratinib, loperamide and budesonide
neratinib and intensive loperamide prophylaxis in combination with budesonide
Drug: Neratinib
neratinib 240 mg (full treatment as extended adjuvant treatment for 13 cycles)
Drug: Loperamide
intensive loperamide prophylaxis for two 28 day cycles (total 56 days) for neratinib and loperamide arm and budesonide arm, or 28 days for colestipol and bismuth subsalicylate or mesalamine arms
Drug: Budesonide
budesonide extended release tablets 9 mg once daily with or without food for 28 days
Experimental: neratinib, loperamide and colestipol
neratinib and intensive loperamide prophylaxis in combination with colestipol
Drug: Neratinib
neratinib 240 mg (full treatment as extended adjuvant treatment for 13 cycles)
Drug: Loperamide
intensive loperamide prophylaxis for two 28 day cycles (total 56 days) for neratinib and loperamide arm and budesonide arm, or 28 days for colestipol and bismuth subsalicylate or mesalamine arms
Drug: Colestipol
colestipol 2 g twice daily with or without food for 28 days
Experimental: neratinib, loperamide and bismuth subsalicylate or mesalamine
neratinib and intensive loperamide prophylaxis in combination with bismuth subsalicylate or mesalamine
Drug: Neratinib
neratinib 240 mg (full treatment as extended adjuvant treatment for 13 cycles)
Drug: Loperamide
intensive loperamide prophylaxis for two 28 day cycles (total 56 days) for neratinib and loperamide arm and budesonide arm, or 28 days for colestipol and bismuth subsalicylate or mesalamine arms
Drug: Bismuth Subsalicylate or Mesalamine
bismuth subsalicylate 262 mg 3 times per day or mesalamine 2.4 g/day with food, for 28 days
Experimental: neratinib, loperamide
neratinib and intensive loperamide prophylaxis
Drug: Neratinib
neratinib 240 mg (full treatment as extended adjuvant treatment for 13 cycles)
Drug: Loperamide
intensive loperamide prophylaxis for two 28 day cycles (total 56 days) for neratinib and loperamide arm and budesonide arm, or 28 days for colestipol and bismuth subsalicylate or mesalamine arms

Detailed Description:

An open-label, Phase 2 study that will investigate the incidence of diarrhea in HER2+ breast cancer patients receiving neratinib with intensive loperamide diarrhea prophylaxis, alone and in combination with anti-inflammatory treatment, who have previously undergone a course of trastuzumab therapy in the adjuvant setting

Patients will receive:

  • Neratinib 240 mg orally once daily for thirteen (13) 28-day cycles
  • Loperamide daily for two (2) 28-day cycles and then as needed, or loperamide for 1 cycle [28 days] starting with the treatment group receiving colestipol under Amendment 4, and then as needed thereafter
  • Either an anti-inflammatory treatment for 1 cycle (for patients enrolled starting with Amendment 3), or a bile acid sequestrant treatment for 1 cycle (starting with the treatment group receiving colestipol under Amendment 4)
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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. Clinical and radiologic assessments that are negative for local or regional recurrence of disease or metastatic disease at the time of study entry, including

    • 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
    • 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
    • Chest radiograph
  7. Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO)
  8. Eastern Cooperative Oncology Group (ECOG) status of 0 to 1
  9. 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.]
  10. 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. Men and their female partners of childbearing potential must agree and commit to use a highly effective method of contraception (ie, any of the above methods or hormonal contraception associated with inhibition of ovulation) while on treatment and for 3 months after last dose of investigational products
  11. Recovery (ie, to Grade 1 or baseline) from all clinically significant AEs related to prior therapies (excluding alopecia, neuropathy, and nail changes)
  12. Provide written, informed consent to participate in the study and follow the study procedures

Exclusion 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, 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) Creatinine Creatinine clearance <30 mL/min (as calculated by Cockcroft-Gault formula or Modification of Diet in Renal Disease [MDRD] formula)

  7. Active, unresolved infections
  8. 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
  9. Currently pregnant or breast-feeding
  10. 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)
  11. Clinically active infection with hepatitis B or hepatitis C virus
  12. 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
  13. 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
  14. Unable or unwilling to swallow tablets
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02400476

Contacts
Contact: Puma Biotechnology, Inc. (424) 248-6500 clinicaltrials@pumabiotechnology.com

  Show 48 Study Locations
Sponsors and Collaborators
Puma Biotechnology, Inc.
  More Information

Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT02400476     History of Changes
Other Study ID Numbers: PUMA-NER-6201
Study First Received: February 17, 2015
Last Updated: June 19, 2017

Keywords provided by Puma Biotechnology, Inc.:
HER2 +
Breast Cancer
Neratinib

Additional relevant MeSH terms:
Breast Neoplasms
Diarrhea
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Budesonide
Mesalamine
Bismuth
Bismuth subsalicylate
Loperamide
Antidiarrheals
Colestipol
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 27, 2017