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
- Conditions
- Early Stage HER2+ Breast Cancer
- Interventions
- Registration Number
- NCT02400476
- Lead Sponsor
- 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 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 563
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Colestipol and Loperamide 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. Loperamide 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. Neratinib Dose Escalation 2 Loperamide 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. Colestipol and Loperamide Neratinib 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. Colestipol with Loperamide as needed Neratinib 240 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 Neratinib 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. Colestipol with Loperamide as needed Colestipol 240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed. Budesonide and Loperamide Neratinib 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. Neratinib Dose Escalation 2 Neratinib 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. Loperamide Neratinib 240 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 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. Budesonide and Loperamide Budesonide 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. Colestipol and Loperamide Colestipol 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. Colestipol with Loperamide as needed Loperamide 240 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 Loperamide 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.
- Primary Outcome Measures
Name Time Method Percentage of Patients With Grade 3 or Higher Diarrhea, According to NCI CTCAE v4.0. From first dose of investigational product through 28 days after last dose, up to 15.5 months. 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.
- Secondary Outcome Measures
Name Time Method 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. Assess the percentage of patients with serious adverse events (SAEs) and other adverse events of special interest (AESI). AESIs were selected based on the known safety profile of neratinib as well as typical key body system toxicity concerns generally reviewed for any new drug. These AESIs were grouped into the following categories: gastrointestinal toxicity (diarrhea and stomatitis), hepatotoxicity, pulmonary toxicity (interstitial lung disease), cardiac toxicity (LVEF decreased), and dermatologic toxicity (rash and nail disorders). The AESIs were analyzed by searching the clinical database for all TEAEs and SAEs using either Standardized MedDRA Queries (SMQs) or, if an applicable SMQ did not exist, a Sponsor-defined list of MedDRA preferred terms.
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. Assess the percentage of patients with diarrhea after the administration of an anti-inflammatory agent, a bile acid sequestrant, or following two different dose-escalation regimens of neratinib, by maximum CTC grade. Grade 1: an increase of \<4 stools per day over baseline; mild increase in ostomy output compared to baseline. Grade 2: Increase of 4 - 6 stools per day over baseline; moderate increase in ostomy output compared to baseline. 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.
Trial Locations
- Locations (57)
Compassionate Care Research Group Inc.
🇺🇸Riverside, California, United States
Emad Ibrahim, M.D., Inc.
🇺🇸Redlands, California, United States
The Oncology Institute of Hope and Innovation
🇺🇸Santa Ana, California, United States
University of Maryland, Greenebaum Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Decatur Memorial Hospital Cancer Care Specialists of Central Illinois
🇺🇸Decatur, Illinois, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
Central Coast Medical Oncology Corporation
🇺🇸Santa Maria, California, United States
Baptist Health Urgent Care Sawgrass
🇺🇸Sunrise, Florida, United States
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Cancer Center of Santa Barbara with Sansum Clinic
🇺🇸Santa Barbara, California, United States
Florida Cancer Research Institute, LLC
🇺🇸Plantation, Florida, United States
Community Cancer Trials of Utah
🇺🇸Ogden, Utah, United States
Clinical Research Alliance, Inc
🇺🇸Lake Success, New York, United States
Mammazentrum HH am Krankenhaus Jerusalem
🇩🇪Hamburg, Germany
Institut Gustave Roussy
🇫🇷Villejuif, France
Good Samaritan Hospital Samaritan Pastega Regional Cancer Center
🇺🇸Corvallis, Oregon, United States
McGill University Health Centre, Cedars Cancer Centre
🇨🇦Montreal, Quebec, Canada
Coastal Bend Cancer Center
🇺🇸Corpus Christi, Texas, United States
Ashford Cancer Centre Research
🇦🇺Kurralta Park, South Australia, Australia
CHU Group Hospitalier Pitié-Salpêtrière, Service d'oncologie Médicale
🇫🇷Paris, France
Universitaetsklinikum Schleswig-Holstein (UKSH), Klinik fuer Gynaekologie und Geburtshilfe, Studienzentrale Gynäkologische Onkologie (SGC) Kiel
🇩🇪Kiel, Germany
Sana Klinikum Offenbach GmbH - Frauenklinik
🇩🇪Offenbach, Germany
Medical University of Vienna, Department of Oncology
🇦🇹Vienna, Austria
Sunnybrook Research Insitute
🇨🇦Toronto, Ontario, Canada
Praxis für interdisziplinäre Onkologie & Hämatologie
🇩🇪Freiburg, Germany
St. Joseph Heritage Healthcare
🇺🇸Fullerton, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Torrance Memorial Physician Network Cancer Care Associates
🇺🇸Redondo Beach, California, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Sydney Adventist Hospital
🇦🇺Wahroonga, New South Wales, Australia
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
Universitaetsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
BCRC-WA, Hollywood Private Hospital
🇦🇺Nedlands, Western Australia, Australia
Cancer Treatment Centers of America
🇺🇸Newnan, Georgia, United States
Jersey Shore University Medical Center
🇺🇸Neptune, New Jersey, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Central Maine Medical Center
🇺🇸Lewiston, Maine, United States
North Mississippi Medical Center Hematology and Oncology Services
🇺🇸Tupelo, Mississippi, United States
MD Anderson Cancer Center at Cooper
🇺🇸Voorhees, New Jersey, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Great Plains Health (Callahan Cancer Center)
🇺🇸North Platte, Nebraska, United States
Univ. Klinik für Innere Medizin, Klin. Abt. Onkologie
🇦🇹Graz, Austria
Saint Joseph / Candler SC Cancer Specialists
🇺🇸Hilton Head Island, South Carolina, United States
Medical University of Innsbruck-Department of Gynecology
🇦🇹Innsbruck, Austria
Medical University of Vienna,Department of Obstetrics and Gynecology
🇦🇹Vienna, Austria
Uniklinikum Salzburg, Landeskrankenhaus, Univ. Klinik fur Innere Medizin III der PMU
🇦🇹Salzburg, Austria
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Magee-Womens Hospital of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Alabama Oncology
🇺🇸Birmingham, Alabama, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Charleston Hematology Oncology Associates
🇺🇸Charleston, South Carolina, United States
Hematology-Oncology Associates of the Treasure Coast
🇺🇸Port Saint Lucie, Florida, United States