Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer

Status:	Completed
Conditions:	Breast Cancer, Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	9/7/2018
Start Date:	December 9, 2008
End Date:	June 2018

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

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.

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.

- 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.

- 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 and 2:

- At least 1 measurable lesion as defined by RECIST criteria.

- 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.

- 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 and 2:

- Subjects with bone as the only site of disease.

- 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.

- 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.

We found this trial at

sites

Dayton Clinical Oncology Program

Dayton, Ohio 45429

from

Dayton, OH