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Study Evaluating HKI-272 (Neratinib) In Subjects With Advanced Breast Cancer

Phase 2
Completed
Conditions
Neoplasms
Breast Neoplasms
Interventions
Registration Number
NCT00300781
Lead Sponsor
Puma Biotechnology, Inc.
Brief Summary

The purpose of this study is to learn whether neratinib is safe and effective in treating women with advanced human epidermal growth factor receptor 2 (HER2) positive breast cancer.

Detailed Description

Arm A: HER2 gene amplification and disease progression following at least 6 weeks of standard doses of Herceptin; Arm B: HER2 gene amplification and no prior Herceptin or HER2-targeted treatment.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
136
Inclusion Criteria
  • Pathologic diagnosis of breast cancer and current stage IIIB, IIIC, or IV
  • Progression following at least 6 weeks of standard doses of Herceptin (Arm A only)
  • Over-expression of HER2
  • Tumor tissue available and adequate for analysis at screening
  • At least one measurable lesion
Exclusion Criteria
  • Prior treatment with Herceptin (Arm B only)
  • More than 4 prior cytotoxic chemotherapy regimens
  • Subjects with bone or skin as the only site of measurable disease
  • Inadequate cardiac function
  • Major surgery, chemotherapy, radiotherapy, investigational agents or other cancer therapy within 1 week of treatment day 1
  • Active central nervous system metastases
  • Pregnant or breastfeeding women
  • Inability to swallow the HKI-272 capsules

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Neratinib 240 mg, with prior trastuzumabneratinibNeratinib administered with 80 mg capsules and 40 mg coated tablets taken orally in prescribed dose of 240 mg daily, as long as tolerated and disease does not worsen.
Neratinib 240 mg, no prior trastuzumabneratinibNeratinib administered with 80 mg capsules and 40 mg coated tablets taken orally in prescribed dose of 240 mg daily, as long as tolerated and disease does not worsen.
Primary Outcome Measures
NameTimeMethod
16-week Progression Free SurvivalFrom first dose to 16 weeks

16 week progression-free survival (PFS) rate of neratinib in women with human epidermal growth factor receptor 2 (HER2) positive breast cancer, either with prior trastuzumab or no prior trastuzumab therapy, evaluated by independent assessment of tumor scans collected at baseline and then every 8 weeks.

Secondary Outcome Measures
NameTimeMethod
Objective Response RateFrom first dose date to progression or last tumor assessment, up to 46 months

Percentage of participants with Partial Response (PR) or Complete Response (CR) by independent assessment of tumor per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Duration of ResponseFrom start date of response to first PD/death, up to 46 months

Number of weeks between Complete Response (CR) or Partial Response (PR) and the first date of disease progression (PD) or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions

Clinical Benefit RateFrom first dose date to progression or last tumor assessment, up to 46 months

Percentage of participants who experienced Complete Response (CR), Partial Response (PR), or Stable Disease (SD) ≥ 24 weeks by independent assessment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.

Trial Locations

Locations (33)

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Boston University Medical Center

🇺🇸

Boston, Massachusetts, United States

The Cleveland Clinic Taussig Cancer Center

🇺🇸

Cleveland, Ohio, United States

The Cancer Center at GBMC

🇺🇸

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

Norris Cotton Cancer Center Dartmouth Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Arke Estudios Clínicos S.A. de C.V.

🇲🇽

Mexico City, Mexico

University of Colorado Hospital

🇺🇸

Aurora, Colorado, United States

Oncology Care Associates

🇺🇸

Bethesda, Maryland, United States

Virginia Mason Medical Center

🇺🇸

Seattle, Washington, United States

Midwestern Regional Medical Center

🇺🇸

Zion, Illinois, United States

Faulkner Hospital

🇺🇸

Boston, Massachusetts, United States

The Cancer Institute of New Jersey

🇺🇸

New Brunswick, New Jersey, United States

St-Augustinus Ziekenhuis Oncology Department

🇧🇪

Wilrijk, Belgium

University Hospital Gasthuisberg

🇧🇪

Leuven, Belgium

Institut Jules Bordet Unite du Chimiotherapie

🇧🇪

Brussels, Belgium

Institut Gustave ROUSSY Service de Pathologie Mammaire

🇫🇷

Villejuif Cedex, France

Cancer Hospital Peking Union Medical College

🇨🇳

Beijing, China

Deenanath Mangeshkar Hospital

🇮🇳

Pune, Maharashtra, India

No. 81 Hospital of Chinese People's Liberation Army

🇨🇳

Nanjing, Jiangsu, China

The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army

🇨🇳

Beijing, Beijing, China

Jehangir Clinical Development Centre

🇮🇳

Pune, Maharashtra, India

Chinese People's Liberation Army General Hospital

🇨🇳

Beijing, China

Nizam's Institute of Medical Sciences

🇮🇳

Hyderabad, Panjagutta, India

Tata Memorial Centre

🇮🇳

Mumbai, Parel, India

Hospital de Especialidades MIG

🇲🇽

Mexico City, Mexico

Hospital Regional Lic. Adolfo Lopez Mateos Oncología Médica

🇲🇽

Mexico City, Mexico

N.N. Blokhin Russian Cancer Research Center of RAMS

🇷🇺

Moscow, Russian Federation

Medical Radiological Research Center of RAMS, Department of Radiation and Surgical Methods

🇷🇺

Obninsk, Russian Federation

City Hospital N 31 Oncology Haematology Dept. For Adults

🇷🇺

Saint Petersburg, Russian Federation

City Oncology Dispensary

🇷🇺

Saint Petersburg, Russian Federation

Breast Tumor Department, N.N. Petrov Research Institute of Oncology

🇷🇺

Saint-Petersburg, Russian Federation

Louisiana State University

🇺🇸

Shreveport, Louisiana, United States

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