Know Cancer

forgot password

A Phase I/II Study of HKI-272 in Combination With Trastuzumab (Herceptin) in Subjects With Advanced Breast Cancer

Phase 1/Phase 2
18 Years
Open (Enrolling)
Advanced Breast Cancer

Thank you

Trial Information

A Phase I/II Study of HKI-272 in Combination With Trastuzumab (Herceptin) in Subjects With Advanced Breast Cancer

Open label phase 1/2 study of ascending multiple oral doses of HKI-272 in combination with
IV Herceptin in subjects with advanced 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 of HKI-272
plus Herceptin is determined, an additional 30 subjects will be enrolled at that dose level,
and followed for progression free survival for approximately 1 year.

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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of participants with adverse events

Outcome Time Frame:

At screening, weekly for the first month, then at weeks 1 and 4 thereafter, and at the final visit

Safety Issue:


Principal Investigator


Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

April 2007

Completion Date:

December 2013

Related Keywords:

  • Advanced Breast Cancer
  • HKI-272
  • neratinib
  • trastuzumab
  • Herceptin
  • breast cancer
  • Breast Neoplasms



Investigational Site Baltimore, Maryland  21204
Investigational Site Duarte, California  91010-3000
Investigational Site Durham, North Carolina  27710
Investigational Site Philadelphia, Pennsylvania  19111