APRiCOT-B: Study to Evaluate Apricoxib in Combination With Lapatinib and Capecitabine in the Treatment of HER2/Neu+ Breast Cancer (TP2001-202)

Study Overview
=================
Brief Summary
-----------------
This study will compare the anti-tumor efficacy of apricoxib and lapatinib/capecitabine with placebo and lapatinib/capecitabine as measured by time to disease progression and evaluate urinary PGE-M measurements or baseline COX-2 expression in tumor tissue by IHC as a surrogate selection criterion for patients who will benefit from future treatment with apricoxib.

Official Title
-----------------
A Phase 2 Study of the Efficacy and Safety of Apricoxib in Combination With Lapatinib and Capecitabine in the Treatment of Patients With HER2/Neu+ Breast Cancer Who Have Failed Trastuzumab and Chemotherapy Including a Taxane

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: apricoxib + lapatinib + capecitabine
* Drug: placebo + lapatinib + capecitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Females with pathologically determined locally advanced or metastatic human epidermal growth factor receptor 2 positive (HER2/neu+) breast cancer Have progressed after treatment with chemotherapy including a taxane and trastuzumab Must have measurable disease by RECIST ECOG PS of 0,1, or 2 MUGA scan or echocardiogram results show left ventricular ejection fraction greater than or equal to 50% Exclusion Criteria: Radiation therapy within 2 weeks, chemotherapy within 3 weeks, or noncytoxic investigational agents within 4 weeks of initiating study treatment Evidence of New York Heart Association class III or greater cardiac disease History of MI, stroke, ventricular arrhythmia, or symptomatic conduction abnormality History of congenital QT prolongation Concurrent severe or uncontrolled medical disease Symptomatic central nervous system metastases Pregnant or nursing women Hypersensitivity or intolerance to apricoxib, lapatinib, capecitabine, 5-FU, sulfonamides, aspirin, or NSAIDs Severe renal insufficiency History of upper GI bleeding, ulceration, or perforation- Concurrent use of potent CYP3A4 inhibitors and CYP3A4 inducers Prior treatment with capecitabine Patients on anti-arrhythmic treatment Prior lapatinib therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>apricoxib + lapatinib + capecitabine | Drug: apricoxib + lapatinib + capecitabine<br>* apricoxib: 100 mg tablets, 400 mg/day lapatinib: per package insert capecitabine: per package insert<br>|
| Placebo Comparator: B<br>placebo + lapatinib + capecitabine | Drug: placebo + lapatinib + capecitabine<br>* placebo: 100 mg tablets, 400 mg/day lapatinib: per package insert capecitabine: per package insert<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the anti-tumor activity of the combination of apricoxib/lapatinib-capecitabine compared with placebo/lapatinib-capecitabine as measured by time to disease progression. |  | Time to disease progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival and safety/tolerability |  | Time to disease progression | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HER2/neu positive, locally advanced or metastatic