Clinical trial NCT00398567: A Phase 1/2 Study Of HKI-272 (Neratinib) in Combination With Trastuzumab (Herceptin) In Subjects With Advanced Breast Cancer
Official title: A Phase I/II Study of HKI-272 in Combination With Trastuzumab (Herceptin) in Subjects With Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Breast Cancer
Keywords: HKI-272
neratinib
trastuzumab
breast cancer
Nerlynx
PB-272
HER2
Lead sponsor: Puma Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2006-11-10
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 16-week Progression-free Survival (PFS) Rate
timeFrame: From first dose date to progression status (PD or death) at 16-week
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From first dose date to progression or last tumor assessment, up to five and a half years.
measure: Duration of Response (DOR)
timeFrame: From start date of response to first PD, assessed up to five and half years after the first subject was randomized
measure: Progression Free Survival (PFS)
timeFrame: From first dose date to progression or death, assessed up to five and half years.
measure: Clinical Benefit Rate (CBR)
timeFrame: From first dose date to progression or last tumor assessment, assessed up to five and half years.
measure: Area Under the Curve of Neratinib Concentration
timeFrame: Prior to the first dose, and at hours 1, 2, 4, 6, 8 and 24 on days 22.
measure: Terminal-phase Elimination Half-life of Neratinib in Combination With Trastuzumab.
timeFrame: Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: LAC/USC Medical Center, USC/Norris Comprehensive Cancer Center
state: California
city: Pasadena
country: United States
facility: City of Hope National Medical Center
state: California
city: Baltimore
country: United States
facility: University of Maryland, University of Maryland Medical Center
state: Maryland
city: Durham
country: United States
facility: Duke University, Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nanjing
country: China
facility: Chinese Nanjing Bayi Hospital
state: Jiangsu
city: Tianjin
country: China
facility: Tianjin Union Medicine Center
state: Tianjin
city: Beijing
country: China
facility: Cancer Hospital, Academy of Med Science and Peking Union Med
city: Beijing
country: China
facility: 307 Hospital of Chinese People's Liberation Army
city: Beijing
country: China
facility: Chinese PLA General Hospital
city: Paris
country: France
facility: Institut Curie
city: Saint-Herblain
country: France
facility: Centre Rene Gauducheau
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
affiliation: Biotechnology
name: Puma
role: STUDY_DIRECTOR
References: