Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02400476
Recruitment Status : Recruiting
First Posted : March 27, 2015
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Brief 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 Loperamide

Condition or disease Intervention/treatment Phase
Early Stage HER2+ Breast Cancer Drug: Neratinib Drug: Loperamide Drug: Colestipol Drug: Budesonide Phase 2

Detailed Description:

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 loperamide, 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.
  • 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. Closed to enrollment.
  • Amendment 4, colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed. Closed to enrollment.
  • Amendment 5, colestipol for 1 cycle and loperamide as needed. Closed to enrollment.
  • Amendment 6/6.1, 120 mg neratinib for Week 1 (C1D1-C1D7), followed by 160 mg neratinib for Week 2 (C1D8- C1D14), followed by 240 mg neratinib for Week 3 and thereafter (C1D15 to end of treatment). Loperamide as needed.
  • Amendment 7, 160 mg neratinib for the first 2 weeks (C1D1 - C1D14), followed by 200 mg neratinib for the next 2 weeks (C1D15 - C1D28), followed by 240 mg neratinib thereafter (C2D1 to end of treatment). Loperamide as needed.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 750 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
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 Loperamide
Actual Study Start Date : February 2015
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : May 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Loperamide
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.
Drug: Neratinib
Other Name: Nerlynx

Drug: Loperamide
Experimental: Budesonide and Loperamide
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter.
Drug: Neratinib
Other Name: Nerlynx

Drug: Loperamide
Drug: Budesonide
9 mg extended release tablets once daily with or without food for 28 days

Experimental: Colestipol and Loperamide
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter.
Drug: Neratinib
Other Name: Nerlynx

Drug: Loperamide
Drug: Colestipol
2 g twice daily with or without food for one 28 day cycle

Experimental: Colestipol with Loperamide as needed
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.
Drug: Neratinib
Other Name: Nerlynx

Drug: Loperamide
Drug: Colestipol
2 g twice daily with or without food for one 28 day cycle

Experimental: Neratinib Dose Escalation (Am 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 (C1D15 to End of Treatment). Loperamide administered as needed.
Drug: Neratinib
Other Name: Nerlynx

Drug: Loperamide
Experimental: Neratinib Dose Escalation (Am 7)
160 mg neratinib for the first 2 weeks, followed by 200 mg neratinib for the next 2 weeks, followed by 240 mg neratinib thereafter (C2D1 to End of treatment. Loperamide will be administered on an as-needed basis only.
Drug: Neratinib
Other Name: Nerlynx

Drug: Loperamide



Primary Outcome Measures :
  1. 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 :
  1. 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)

  2. Incidence and severity of diarrhea [ Time Frame: Length of study (15 months) ]
    Assess the incidence and severity of diarrhea after the administration of an anti-inflammatory agent, a bile acid sequestrant, or following two different dose-escalation regimens of neratinib



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18; male or female, early breast cancer (stage I-3c)
  • Documented HER2+ tumor1: HER2 immunohistochemistry (IHC) 3+ or ISH+
  • Prior course of adjuvant trastuzumab given >2 weeks and ≤1 from enrollment
  • No evidence of local/regional recurrence or metastatic disease
  • Radiologic assessment (Chest X-ray at a minimum) others if abnormal labs during screening
  • Eastern Cooperative Oncology Group (ECOG) PS ≤1 (0 or 1)
  • Endocrine therapy and other prior HER2-directed therapy, including pertuzumab, TDM-1 is permitted
  • Male patient with female partners of childbearing potential must agree and commit to use a condom and Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception

Exclusion Criteria:

  • Major surgery < 30 days
  • Chemotherapy, investigational agents, other cancer therapy < 14 days
  • Normal Left Ventricular Ejection Fraction (LVEF) < 50%, Corrected QT Interval (QTc) >0.450 seconds (males) or >0.470 (females) or other active cardiac disease
  • Significant chronic GI disorder with diarrhea as a major symptom
  • No evidence of metastatic breast cancer with negative chest x-ray and other imaging if abnormal lab value

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02400476


Contacts
Layout table for location contacts
Contact: Puma Biotechnology, Inc. (424) 248-6500 clinicaltrials@pumabiotechnology.com

  Show 59 Study Locations
Sponsors and Collaborators
Puma Biotechnology, Inc.
Investigators
Layout table for investigator information
Study Director: Clinical Development Chief Medical and Scientific Officer Puma Biotechnology, Inc.

Layout table for additonal information
Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT02400476     History of Changes
Other Study ID Numbers: PUMA-NER-6201
2015-004374-15 ( EudraCT Number )
First Posted: March 27, 2015    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Puma Biotechnology, Inc.:
HER2 +
Breast Cancer
Neratinib
Nerlynx
Loperamide
Colestipol
Budesonide
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Diarrhea
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Budesonide
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
Gastrointestinal Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Sequestering Agents