Overview

This trial is active, not recruiting.

Condition advanced breast cancer
Treatments hki-272, herceptin
Phase phase 1/phase 2
Targets HER2, EGFR
Sponsor Puma Biotechnology, Inc.
Start date April 2007
End date July 2009
Trial size 45 participants
Trial identifier NCT00398567, 3144A1-202, B1891013

Summary

The purpose of this study is to learn whether it is safe and effective to administer HKI-272 (neratinib) in combination with Herceptin in patients with advanced breast cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
All subjects receiving HKI-272 (neratinib) in combination with trastuzumab (Herceptin)
hki-272 neratinib
neratinib 160 mg daily by mouth
herceptin trastuzumab
Herceptin 4 mg/kg IV as a loading dose followed by Herceptin 2 mg/kg weekly thereafter
(Experimental)
All subjects receiving HKI-272 (neratinib) in combination with trastuzumab (Herceptin)
hki-272 neratinib
neratinib 160 mg daily by mouth
herceptin trastuzumab
Herceptin 4 mg/kg IV as a loading dose followed by Herceptin 2 mg/kg weekly thereafter
(Experimental)
All subjects receiving HKI-272 (neratinib) in combination with trastuzumab (Herceptin)
hki-272 neratinib
neratinib 240 mg daily by mouth
herceptin trastuzumab
Herceptin 4 mg/kg IV as a loading dose followed by Herceptin 2 mg/kg weekly thereafter

Primary Outcomes

Measure
Number of participants with adverse events
time frame: At screening, weekly for the first month, then at weeks 1 and 4 thereafter, and at the final visit
Objective response rate
time frame: At screening and then every 2 months throughout the study

Secondary Outcomes

Measure
Observed maximum concentration of HKI-272 (neratinib)
time frame: Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6
Time of maximum concentration of HKI-272 (neratinib)
time frame: Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6
Area under the plasma concentration versus time curve of HKI-272 (neratinib)
time frame: Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase I/II Study of HKI-272 in Combination With Trastuzumab (Herceptin) in Subjects With Advanced Breast Cancer
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2014.
Information provided to ClinicalTrials.gov by Puma Biotechnology, Inc..