Clinical trial NCT02400476: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Early Stage HER2+ Breast Cancer
Keywords: HER2 +
Breast Cancer
Neratinib
Nerlynx
Loperamide
Colestipol
Budesonide
Lead sponsor: Puma Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2015-03-27
Enrollment: 563
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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, or neratinib dose escalation, 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 28-day cycles.
* Loperamide daily for two 28-day cycles and then as needed.
* Amendment 3, an anti-inflammatory treatment for one cycle and loperamide to be administered daily for two 28-day cycles and then as needed. Closed to enrollment.
* Amendment 4, colestipol for one cycle and loperamide to be administered one cycle and then as needed. Closed to enrollment.
* Amendment 5, colestipol for one 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. Closed to enrollment.
* Amendment 7/7.1, 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Patients With Grade 3 or Higher Diarrhea, According to NCI CTCAE v4.0.
timeFrame: From first dose of investigational product through 28 days after last dose, up to 15.5 months.
Secondary outcomes:
measure: Percentage of Patients With Diarrhea by Grade, According to the National Cancer Institute Common Terminology Criteria (NCI CTCAE), Version 4.0.
timeFrame: From first dose of investigational product through 28 days after last dose, up to 15.5 months.
measure: Percentage of Patients With Serious Adverse Events and Other Adverse Events of Special Interest
timeFrame: From first dose of investigational product through 28 days after last dose, up to 15.5 months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology
state: Alabama
city: Corona
country: United States
facility: Compassionate Care Research Group Inc.
state: California
city: Fullerton
country: United States
facility: St. Joseph Heritage Healthcare
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Redlands
country: United States
facility: Emad Ibrahim, M.D., Inc.
state: California
city: Redondo Beach
country: United States
facility: Torrance Memorial Physician Network Cancer Care Associates
state: California
city: Riverside
country: United States
facility: Compassionate Care Research Group Inc.
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Santa Ana
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Santa Barbara
country: United States
facility: Cancer Center of Santa Barbara with Sansum Clinic
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Plantation
country: United States
facility: Florida Cancer Research Institute, LLC
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology-Oncology Associates of the Treasure Coast
state: Florida
city: Sunrise
country: United States
facility: Baptist Health Urgent Care Sawgrass
state: Florida
city: Newnan
country: United States
facility: Cancer Treatment Centers of America
state: Georgia
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Specialists of Central Illinois
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Lewiston
country: United States
facility: Central Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Comprehensive Cancer Center
state: Maryland
city: Tupelo
country: United States
facility: North Mississippi Medical Center Hematology and Oncology Services
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: North Platte
country: United States
facility: Great Plains Health (Callahan Cancer Center)
state: Nebraska
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Voorhees
country: United States
facility: MD Anderson Cancer Center at Cooper
state: New Jersey
city: Lake Success
country: United States
facility: Clinical Research Alliance, Inc
state: New York
city: Corvallis
country: United States
facility: Good Samaritan Hospital Samaritan Pastega Regional Cancer Center
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates
state: South Carolina
city: Hilton Head Island
country: United States
facility: Saint Joseph / Candler SC Cancer Specialists
state: South Carolina
city: Corpus Christi
country: United States
facility: Coastal Bend Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Ogden
country: United States
facility: Community Cancer Trials of Utah
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Wahroonga
country: Australia
facility: Sydney Adventist Hospital
state: New South Wales
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research
state: South Australia
city: Nedlands
country: Australia
facility: BCRC-WA, Hollywood Private Hospital
state: Western Australia
city: Graz
country: Austria
facility: Univ. Klinik für Innere Medizin, Klin. Abt. Onkologie
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck-Department of Gynecology
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg, Landeskrankenhaus, Univ. Klinik fur Innere Medizin III der PMU
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Oncology
city: Vienna
country: Austria
facility: Medical University of Vienna,Department of Obstetrics and Gynecology
city: Toronto
country: Canada
facility: Sunnybrook Research Insitute
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre, Cedars Cancer Centre
state: Quebec
city: Paris
country: France
facility: CHU Group Hospitalier Pitié-Salpêtrière, Service d'oncologie Médicale
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Freiburg
country: Germany
facility: Praxis für interdisziplinäre Onkologie & Hämatologie
city: Hamburg
country: Germany
facility: Mammazentrum HH am Krankenhaus Jerusalem
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein (UKSH), Klinik fuer Gynaekologie und Geburtshilfe, Studienzentrale Gynäkologische Onkologie (SGC) Kiel
city: Offenbach
country: Germany
facility: Sana Klinikum Offenbach GmbH - Frauenklinik
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: Puma Biotechnology, Inc.
name: Chief Scientific Officer
role: STUDY_DIRECTOR
References:
citation: Barcenas 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.