A Phase 1/2 Study Of HKI-272 (Neratinib) in Combination With Trastuzumab (Herceptin) In Subjects With Advanced Breast Cancer

NCT ID: NCT00398567

Last Updated: 2018-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-04
• Study Completion Date: 2018-03-02

Brief Summary

The purpose of this study is to determine the safety and efficacy of HKI-272 (neratinib) in combination with trastuzumab in patients with advanced breast cancer.

Detailed Description

Open label phase 1/2 study of ascending multiple oral doses of HKI-272 in combination with IV trastuzumab in subjects with advanced human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Three to six subjects will be enrolled in each dose group. Adverse events and dose limiting toxicities will be assessed from the first dose of study drug though day 21. When the maximum tolerated dose (MTD) of HKI-272 plus trastuzumab is determined, an additional 30 subjects will be enrolled at that dose level, and followed for progression free survival for approximately 1 year.

Conditions

Advanced Breast Cancer

Study Design

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

Study Groups

Part 1 - dose level 1 (160 mg)

All subjects receiving HKI-272 dose level 1 in combination with trastuzumab

Group Type: EXPERIMENTAL

HKI-272

Intervention Type: DRUG

HKI-272 by mouth

trastuzumab

Intervention Type: DRUG

trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter

Part 1 - dose level 2 (240 mg)

All subjects receiving HKI-272 dose level 2 in combination with trastuzumab

Group Type: EXPERIMENTAL

HKI-272

Intervention Type: DRUG

HKI-272 by mouth

trastuzumab

Intervention Type: DRUG

trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter

Part 2 - expanded MTD cohort

All subjects receiving HKI-272 in combination with trastuzumab

Group Type: EXPERIMENTAL

HKI-272

Intervention Type: DRUG

HKI-272 by mouth

trastuzumab

Intervention Type: DRUG

trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter

Interventions

HKI-272

HKI-272 by mouth

Intervention Type: DRUG

trastuzumab

trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter

Intervention Type: DRUG

Other Intervention Names

neratinib; Herceptin

Eligibility Criteria

Inclusion Criteria

• Pathologic diagnosis of breast cancer with current stage IIIB, IIIC or IV not curable by available therapy
• Progression following at least one Herceptin-containing cytotoxic chemotherapy regimen (neoadjuvant, adjuvant, or metastatic setting)
• HER2 positive breast cancer
• At least one measurable target lesion
• Adequate performance status
• Adequate cardiac, kidney, and liver function
• Adequate blood counts
• Willingness of all subjects who are not surgically sterile or post menopausal to use acceptable methods of birth control

Exclusion Criteria

• More than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease
• Major surgery, chemotherapy, radiotherapy, investigational agents, Herceptin or other cancer therapy within 2 weeks of treatment day 1
• Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2
• Extensive visceral disease
• Active central nervous system metastases
• Pregnant or breast feeding women
• Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom
• Prior exposure to HKI-272 or other HER2 targeted agents (except Herceptin and Tykerb)
• Significant cardiac disease or dysfunction
• History of life-threatening hypersensitivity to Herceptin
• Inability or unwillingness to swallow HKI-272 capsules
• Any other cancer within 5 years with the exception of contralateral breast cancer, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin

• 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

Puma

Role: STUDY_DIRECTOR

Biotechnology

Locations

City of Hope National Medical Center

Duarte, California, United States

LAC/USC Medical Center, USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

City of Hope National Medical Center

Pasadena, California, United States

University of Maryland, University of Maryland Medical Center

Baltimore, Maryland, United States

Duke University, Duke University Medical Center

Durham, North Carolina, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Chinese Nanjing Bayi Hospital

Nanjing, Jiangsu, China

Tianjin Union Medicine Center

Tianjin, Tianjin Municipality, China

Cancer Hospital, Academy of Med Science and Peking Union Med

Beijing, , China

307 Hospital of Chinese People's Liberation Army

Beijing, , China

Chinese PLA General Hospital

Beijing, , China

Institut Curie

Paris, , France

Centre Rene Gauducheau

Saint-Herblain, , France

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Countries

United States; China; France; Switzerland

Other Identifiers

3144A1-202 / B1891013

Identifier Type: -

Identifier Source: org_study_id