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

NCT ID: NCT02400476

Last Updated: 2022-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 563 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2021-04-22

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.

Conditions

Early Stage HER2+ Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Neratinib

Intervention Type: DRUG

Loperamide

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

Neratinib

Intervention Type: DRUG

Loperamide

Intervention Type: DRUG

Budesonide

Intervention Type: DRUG

9 mg extended release tablets once daily with or without food for 28 days

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.

Group Type: EXPERIMENTAL

Neratinib

Intervention Type: DRUG

Loperamide

Intervention Type: DRUG

Colestipol

Intervention Type: DRUG

2 g twice daily with or without food for one 28 day cycle

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.

Group Type: EXPERIMENTAL

Neratinib

Intervention Type: DRUG

Loperamide

Intervention Type: DRUG

Colestipol

Intervention Type: DRUG

2 g twice daily with or without food for one 28 day cycle

Neratinib Dose Escalation 1

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.

Group Type: EXPERIMENTAL

Neratinib

Intervention Type: DRUG

Loperamide

Intervention Type: DRUG

Neratinib Dose Escalation 2

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.

Group Type: EXPERIMENTAL

Neratinib

Intervention Type: DRUG

Loperamide

Intervention Type: DRUG

Interventions

Neratinib

Intervention Type: DRUG

Loperamide

Intervention Type: DRUG

Colestipol

2 g twice daily with or without food for one 28 day cycle

Intervention Type: DRUG

Budesonide

9 mg extended release tablets once daily with or without food for 28 days

Intervention Type: DRUG

Other Intervention Names

Nerlynx

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Puma Biotechnology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chief Scientific Officer

Role: STUDY_DIRECTOR

Puma Biotechnology, Inc.

Locations

Alabama Oncology

Birmingham, Alabama, United States

Compassionate Care Research Group Inc.

Corona, California, United States

St. Joseph Heritage Healthcare

Fullerton, California, United States

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Emad Ibrahim, M.D., Inc.

Redlands, California, United States

Torrance Memorial Physician Network Cancer Care Associates

Redondo Beach, California, United States

Compassionate Care Research Group Inc.

Riverside, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

The Oncology Institute of Hope and Innovation

Santa Ana, California, United States

Cancer Center of Santa Barbara with Sansum Clinic

Santa Barbara, California, United States

Central Coast Medical Oncology Corporation

Santa Maria, California, United States

Memorial Healthcare System

Hollywood, Florida, United States

Florida Cancer Research Institute, LLC

Plantation, Florida, United States

Hematology-Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, United States

Baptist Health Urgent Care Sawgrass

Sunrise, Florida, United States

Cancer Treatment Centers of America

Newnan, Georgia, United States

Decatur Memorial Hospital Cancer Care Specialists of Central Illinois

Decatur, Illinois, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Central Maine Medical Center

Lewiston, Maine, United States

University of Maryland, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

North Mississippi Medical Center Hematology and Oncology Services

Tupelo, Mississippi, United States

Washington University School of Medicine

St Louis, Missouri, United States

Great Plains Health (Callahan Cancer Center)

North Platte, Nebraska, United States

Saint Barnabas Medical Center

Livingston, New Jersey, United States

Jersey Shore University Medical Center

Neptune City, New Jersey, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

MD Anderson Cancer Center at Cooper

Voorhees Township, New Jersey, United States

Clinical Research Alliance, Inc

Lake Success, New York, United States

Good Samaritan Hospital Samaritan Pastega Regional Cancer Center

Corvallis, Oregon, United States

Providence Portland Medical Center

Portland, Oregon, United States

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Charleston Hematology Oncology Associates

Charleston, South Carolina, United States

Saint Joseph / Candler SC Cancer Specialists

Hilton Head Island, South Carolina, United States

Coastal Bend Cancer Center

Corpus Christi, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Community Cancer Trials of Utah

Ogden, Utah, United States

Utah Cancer Specialists

Salt Lake City, Utah, United States

Inova Schar Cancer Institute

Fairfax, Virginia, United States

Sydney Adventist Hospital

Wahroonga, New South Wales, Australia

Ashford Cancer Centre Research

Kurralta Park, South Australia, Australia

BCRC-WA, Hollywood Private Hospital

Nedlands, Western Australia, Australia

Univ. Klinik für Innere Medizin, Klin. Abt. Onkologie

Graz, , Austria

Medical University of Innsbruck-Department of Gynecology

Innsbruck, , Austria

Uniklinikum Salzburg, Landeskrankenhaus, Univ. Klinik fur Innere Medizin III der PMU

Salzburg, , Austria

Medical University of Vienna, Department of Oncology

Vienna, , Austria

Medical University of Vienna,Department of Obstetrics and Gynecology

Vienna, , Austria

Sunnybrook Research Insitute

Toronto, Ontario, Canada

McGill University Health Centre, Cedars Cancer Centre

Montreal, Quebec, Canada

CHU Group Hospitalier Pitié-Salpêtrière, Service d'oncologie Médicale

Paris, , France

Institut Gustave Roussy

Villejuif, , France

Praxis für interdisziplinäre Onkologie & Hämatologie

Freiburg im Breisgau, , Germany

Mammazentrum HH am Krankenhaus Jerusalem

Hamburg, , Germany

Universitaetsklinikum Schleswig-Holstein

Kiel, , Germany

Universitaetsklinikum Schleswig-Holstein (UKSH), Klinik fuer Gynaekologie und Geburtshilfe, Studienzentrale Gynäkologische Onkologie (SGC) Kiel

Kiel, , Germany

Sana Klinikum Offenbach GmbH - Frauenklinik

Offenbach, , Germany

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Countries

United States; Australia; Austria; Canada; France; Germany; Spain

References

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.

Reference Type: DERIVED

PMID: 36702070 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32464281 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2015-004374-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PUMA-NER-6201

Identifier Type: -

Identifier Source: org_study_id