This trial is active, not recruiting.

Condition breast cancer
Treatments neratinib, capecitabine
Phase phase 1/phase 2
Targets HER2, EGFR
Sponsor Puma Biotechnology, Inc.
Start date December 2008
End date November 2010
Trial size 105 participants
Trial identifier NCT00741260, 3144A1-2206, B1891017


This is a world wide phase 1/2, open-label, study of neratinib in combination with capecitabine, conducted in 2 parts.

In Part 1, 3 to 9 subjects with solid tumors will be enrolled in each dose group of the combination of neratinib and capecitabine. Each subject will participate in only 1 dose group.

Additional subjects may be included at any dose level to further assess the safety and tolerability at that dose level.

In Part 2, up to 60 subjects with erbB-2 positive metastatic breast cancer will receive treatment with the combination of neratinib and capecitabine at the maximum tolerated dose level, as determined in Part 1. In addition 20 subjects with prior lapatinib exposure will be enrolled in Part 2.

Depending on the safety and activity profile observed during the dose escalation phase, the dose selected for Part 2 may be adjusted, if appropriate. In case one test article of the combination is discontinued due to intolerance the other test article can be administered alone.

The primary objectives of Part 1 are to assess the safety and tolerability, and to define the Maximum tolerated dose (MTD) of neratinib in combination with capecitabine in subjects with advanced solid tumors.

The primary objective of Part 2 of this study is to confirm the MTD determined in Part 1.

The secondary objective of Part 1 is to collect information on preliminary anti-tumor activity of the combination of neratinib and capecitabine.

Secondary objectives for Part 2 are to collect pharmacokinetic information and to obtain additional efficacy data, such as Objective Response Rate, for subjects with erbB-2 positive breast cancer treated at the MTD of neratinib + capecitabine.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Neratinib and capecitabine
Neratinib 240mg, continuous daily
capecitabine Xeloda
1500mg/m² of Capecitabine, on days 1-14 of each 21 day cycle.

Primary Outcomes

Investigator assessed radiology review
time frame: until documented Progression of Disease

Secondary Outcomes

Dose Limiting Toxicities; Pharmacokinetics and site-reported efficacy
time frame: until documented Progression of Disease

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Part 1: confirmed pathologic diagnosis of a solid tumor not curable with available therapies for which neratinib plus capecitabine is a reasonable treatment option. - Part 2: confirmed histologically and/or cytologically confirmed diagnosis of breast cancer, metastatic or locally advanced. - Part 2: erbB-2 gene amplified tumor (FISH or CISH) or erbB-2 overexpression (IHC 3+, or IHC2+ with FISH or CISH confirmation), based on local testing, or based on centralized FISH testing prior to day 1. - Part 2: disease progression on or following at least 1 prior trastuzumab containing treatment regimen (at least 6 weeks) for metastatic or locally advanced disease. (Prior adjuvant trastuzumab is allowed but not required). A 2 week period is required between the last dose of trastuzumab treatment and first dose of the test article. - Prior treatment with a taxane in the neoadjuvant, adjuvant, locally advanced, and/or metastatic disease treatment setting. - Parts 1+2: At least 1 measurable lesion as defined by RECIST criteria. - Parts 1+2: LVEF within institutional range of normal as measured by multi-gated acquisition (MUGA) or echocardiogram (ECHO). Exclusion Criteria: - Part 2: prior treatment with capecitabine, lapatinib (20 subjects with prior lapatinib exposure will be enrolled) or any erbB-2 targeted agents except trastuzumab. Treatment with erbB-2 targeted therapy must exceed 2 weeks (14 days) in order to be exclusionary. - Part 2: prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater than 400 mg/m2, epirubicin dose of greater than 800 mg/m2, or the equivalent dose for other anthracyclines. - Parts 1+2: Subjects with bone as the only site of disease. - Parts 1+2: Active uncontrolled or symptomatic central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Subjects with a history of CNS metastases or cord compression are allowable if they have been considered definitively treated and are off anticonvulsants and steroids for at least 4 weeks before the first dose of test article. - Parts 1+2: Any other cancer within 5 years prior to screening with the exception of adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.

Additional Information

Official title A Phase 1/2, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Subjects With Solid Tumors And ErbB-2 Positive Metastatic Or Locally Advanced Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Puma Biotechnology, Inc..
Location data was received from the National Cancer Institute and was last updated in June 2016.