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
2 other identifiers
interventional
563
6 countries
55
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 or other prophylactic measures.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2015
Longer than P75 for phase_2
55 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2015
CompletedFirst Submitted
Initial submission to the registry
February 17, 2015
CompletedFirst Posted
Study publicly available on registry
March 27, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 22, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 22, 2021
CompletedResults Posted
Study results publicly available
May 6, 2022
CompletedMay 6, 2022
January 1, 2021
6.2 years
February 17, 2015
February 28, 2022
April 12, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Patients With Grade 3 or Higher Diarrhea, According to NCI CTCAE v4.0.
The primary objective of this study is to characterize the percentage of patients with Grade 3 or higher 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. Grade 3: Increase of \>=7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death.
From first dose of investigational product through 28 days after last dose, up to 15.5 months.
Secondary Outcomes (2)
Percentage of Patients With Diarrhea by Grade, According to the National Cancer Institute Common Terminology Criteria (NCI CTCAE), Version 4.0.
From first dose of investigational product through 28 days after last dose, up to 15.5 months.
Percentage of Patients With Serious Adverse Events and Other Adverse Events of Special Interest
From first dose of investigational product through 28 days after last dose, up to 15.5 months.
Study Arms (6)
Loperamide
EXPERIMENTAL240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.
Budesonide and Loperamide
EXPERIMENTAL240 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.
Colestipol and Loperamide
EXPERIMENTAL240 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.
Colestipol with Loperamide as needed
EXPERIMENTAL240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.
Neratinib Dose Escalation 1
EXPERIMENTAL120 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.
Neratinib Dose Escalation 2
EXPERIMENTAL160 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.
Interventions
2 g twice daily with or without food for one 28 day cycle
9 mg extended release tablets once daily with or without food for 28 days
Eligibility Criteria
You may qualify if:
- Age ≥18; male or female
- Early breast cancer (stage I-3c)
- Documented HER2+ tumor: HER2 immunohistochemistry (IHC) 3+ or ISH+
- Prior course of adjuvant trastuzumab given \>2 weeks and ≤1 year from enrollment
- No evidence of local/regional recurrence or metastatic disease
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
- Male patients with female partners of childbearing potential must agree and commit to use a condom and women of childbearing potential must not be pregnant and must agree and commit to the use of a highly effective non-hormonal method of contraception
- Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or ECHO
You may not qualify if:
- Major surgery \< 30 days
- Chemotherapy, investigational agents, other cancer therapy (except hormonal therapy) \< 14 days
- 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
- Active, unresolved infections
- Currently pregnant or breast-feeding
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (58)
Alabama Oncology
Birmingham, Alabama, 35205, United States
Compassionate Care Research Group Inc.
Corona, California, 92879, United States
St. Joseph Heritage Healthcare
Fullerton, California, 92835, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095, United States
Emad Ibrahim, M.D., Inc.
Redlands, California, 92373, United States
Torrance Memorial Physician Network Cancer Care Associates
Redondo Beach, California, 90277, United States
Compassionate Care Research Group Inc.
Riverside, California, 92501, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115, United States
The Oncology Institute of Hope and Innovation
Santa Ana, California, 92705, United States
Cancer Center of Santa Barbara with Sansum Clinic
Santa Barbara, California, 93105, United States
Central Coast Medical Oncology Corporation
Santa Maria, California, 93454, United States
Memorial Healthcare System
Hollywood, Florida, 33021, United States
Florida Cancer Research Institute, LLC
Plantation, Florida, 33324, United States
Hematology-Oncology Associates of the Treasure Coast
Port Saint Lucie, Florida, 34952, United States
Baptist Health Urgent Care Sawgrass
Sunrise, Florida, 33322, United States
Cancer Treatment Centers of America
Newnan, Georgia, 30265, United States
Decatur Memorial Hospital Cancer Care Specialists of Central Illinois
Decatur, Illinois, 62526, United States
Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
Norton Cancer Institute
Louisville, Kentucky, 40202, United States
Central Maine Medical Center
Lewiston, Maine, 04240, United States
University of Maryland, Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201, United States
North Mississippi Medical Center Hematology and Oncology Services
Tupelo, Mississippi, 38801, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Great Plains Health (Callahan Cancer Center)
North Platte, Nebraska, 69101, United States
Saint Barnabas Medical Center
Livingston, New Jersey, 07039, United States
Jersey Shore University Medical Center
Neptune City, New Jersey, 07753, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
MD Anderson Cancer Center at Cooper
Voorhees Township, New Jersey, 08035, United States
Clinical Research Alliance, Inc
Lake Success, New York, 11042, United States
Good Samaritan Hospital Samaritan Pastega Regional Cancer Center
Corvallis, Oregon, 97330, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213, United States
Charleston Hematology Oncology Associates
Charleston, South Carolina, 29414, United States
Saint Joseph / Candler SC Cancer Specialists
Hilton Head Island, South Carolina, 29926, United States
Coastal Bend Cancer Center
Corpus Christi, Texas, 78412, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Community Cancer Trials of Utah
Ogden, Utah, 84405, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84106, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
Sydney Adventist Hospital
Wahroonga, New South Wales, Australia
Ashford Cancer Centre Research
Kurralta Park, South Australia, 5037, Australia
BCRC-WA, Hollywood Private Hospital
Nedlands, Western Australia, 6009, Australia
Univ. Klinik für Innere Medizin, Klin. Abt. Onkologie
Graz, 8036, Austria
Medical University of Innsbruck-Department of Gynecology
Innsbruck, A-6020, Austria
Uniklinikum Salzburg, Landeskrankenhaus, Univ. Klinik fur Innere Medizin III der PMU
Salzburg, A-5020, Austria
Medical University of Vienna, Department of Oncology
Vienna, 1090, Austria
Medical University of Vienna,Department of Obstetrics and Gynecology
Vienna, 1090, Austria
Sunnybrook Research Insitute
Toronto, Ontario, M4N3M5, Canada
McGill University Health Centre, Cedars Cancer Centre
Montreal, Quebec, H4A 3J1, Canada
CHU Group Hospitalier Pitié-Salpêtrière, Service d'oncologie Médicale
Paris, 5013, France
Institut Gustave Roussy
Villejuif, 94800, France
Praxis für interdisziplinäre Onkologie & Hämatologie
Freiburg im Breisgau, 79110, Germany
Mammazentrum HH am Krankenhaus Jerusalem
Hamburg, 20357, Germany
Universitaetsklinikum Schleswig-Holstein
Kiel, 24105, Germany
Universitaetsklinikum Schleswig-Holstein (UKSH), Klinik fuer Gynaekologie und Geburtshilfe, Studienzentrale Gynäkologische Onkologie (SGC) Kiel
Kiel, D-24106, Germany
Sana Klinikum Offenbach GmbH - Frauenklinik
Offenbach, 63069, Germany
Hospital Clinico San Carlos
Madrid, 28040, Spain
Hospital Universitario Virgen del Rocio
Seville, 41013, Spain
Related Publications (2)
Chan A, Ruiz-Borrego M, Marx G, Chien AJ, Rugo HS, Brufsky A, Thirlwell M, Trudeau M, Bose R, Garcia-Saenz JA, Egle D, Pistilli B, Wassermann J, Cheong KA, Schnappauf B, Semsek D, Singer CF, Foruzan N, DiPrimeo D, McCulloch L, Hurvitz SA, Barcenas CH. Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer. Breast. 2023 Feb;67:94-101. doi: 10.1016/j.breast.2022.12.003. Epub 2022 Dec 14.
PMID: 36702070DERIVEDBarcenas CH, Hurvitz SA, Di Palma JA, Bose R, Chien AJ, Iannotti N, Marx G, Brufsky A, Litvak A, Ibrahim E, Alvarez RH, Ruiz-Borrego M, Chan N, Manalo Y, Kellum A, Trudeau M, Thirlwell M, Garcia Saenz J, Hunt D, Bryce R, McCulloch L, Rugo HS, Tripathy D, Chan A; CONTROL Study Investigators. Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial. Ann Oncol. 2020 Sep;31(9):1223-1230. doi: 10.1016/j.annonc.2020.05.012. Epub 2020 May 25.
PMID: 32464281DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Director, Clinical Operations
- Organization
- Puma Biotechnology, Inc.
Study Officials
- STUDY DIRECTOR
Chief Scientific Officer
Puma Biotechnology, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 17, 2015
First Posted
March 27, 2015
Study Start
February 1, 2015
Primary Completion
April 22, 2021
Study Completion
April 22, 2021
Last Updated
May 6, 2022
Results First Posted
May 6, 2022
Record last verified: 2021-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- Clinical study documents and clinical trial data may be requested by qualified researchers and study participants for studies that have been completed for at least 18 months, and for which the indication of the drug has been approved in the US and/or EU, as applicable. Requests will be accepted for up to 24 months after the criteria described in this section are met.
- Access Criteria
- Requestors must provide organizational contact information; a detailed research plan, including outcomes; timeline for completion of the research; qualifications of the research team; funding source; and potential conflicts of interest. Puma will not provide access to patient-level data if there is a reasonable likelihood that individual patients could be identified, or in cases where confidentiality or consent provisions prohibit transfer of data or information to third parties. Additionally, Puma will not disclose information that jeopardizes intellectual property rights or divulges confidential commercial information.
Puma Biotechnology is committed to sharing clinical trial data and information to help physicians and patients make informed treatment decisions, and to help qualified researchers advance scientific knowledge. In accordance with legal and regulatory requirements, Puma publishes study protocol information and clinical study results on clinical trial registries, including ClinicalTrials.gov and EU Clinical Trials Register. Puma also publishes information about clinical studies in peer-reviewed scientific journals and shares data in scientific meetings. Puma commits to safeguarding confidentiality and patient privacy throughout the clinical trial data and information sharing process. Any patient-level data will be anonymized to protect personally identifiable information. Qualified researchers and study participants may submit requests for other study documentation and clinical trial data to clinicaltrials@pumabiotechnology.com for consideration.