ELBA: Exemestane and Lapatinib in Advanced Breast Cancer

Study Overview
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Brief Summary
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Aromatase inhibitors are the standard treatment for hormone responsive advanced breast cancer. The combination of the aromatase inhibitor exemestane with with another breast cancer drug that blocks epidermal growth factor receptor (EGFR) and Erb-2 activity (lapatinib) is being studied for the possibility of improving response to therapy, and delaying resistance to endocrine therapy.

Detailed Description
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The recommended dose of lapatinib will be determined in the first part of the study. In the second part of the study, patients will receive the recommended dose of lapatinib and exemestane daily, taken orally.

Official Title
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Phase II Multicentered Study of Exemestane and Lapatinib in Advanced Hormone-responsive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: exemestane
* Drug: lapatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological diagnosis of breast cancer Indication for hormonal therapy (ER and/or PgR positive) Stage IV disease Female gender Postmenopausal status (patients treated with LHRH analogs are eligible for the Phase II part of the study) At least one target or non-target lesion according to RECIST criteria ECOG Performance Status 0-2 Adequate bone marrow (neutrophils > or = 1.500/mm³, platelets > or = 100.000/mm³ and hemoglobin > or = 9 g/dl), hepatic (GOT, GPT < 2.5 e bilirubin <1.25 times the value of upper normal limit) and renal (creatinine < 1.25 times the value of upper normal limit) function Adequate cardiac function (FEVS > or = 50%) Able to take oral medications Life expectancy > 3 months Signed informed consent Exclusion Criteria: Any previous hormone therapy for metastatic disease More than one line of chemotherapy for metastatic disease (first line chemotherapy is permitted) Symptomatic cerebral metastases Planned concomitant radiation therapy in the first month of therapy (for those patients participating in the dose finding phase of the study) Previous therapy with exemestane, including as adjuvant therapy (previous therapy with non-steroidal aromatase inhibitors is permitted) Previous or concurrent malignancy in past 5 years (excluding adequately treated basal cel or spinocellular skin cancer and in situ carcinoma of the cervix) Treatment with experimental pharmacologic therapy within 4 weeks of enrollment in the study Unable or unwilling to provide signed informed consent Any concurrent illness that would, in the Investigator's opinion, contraindicate the use of the study drugs. Active infection Assumption of CYP3A4 inhibitors or inducers (ketoconazole, itraconazole, fluconazole, macrolide antibiotics, antidepressives, calcium-antagonists, cimetidine, carbamazepine, phenytoin, barbiturates, rifampicin e glucocorticoids) Pregnancy or lactation Unable to comply with follow-up Active hepatobiliary disease (with the exception of Gilbert's syndrome, asymptomatic biliary calculi, hepatic metastases or stabile chronic hepatopathy)
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>phase II | Drug: exemestane<br>* 25 mg daily<br>Drug: lapatinib<br>* taken orally, daily, at dose recommended after dose finding part of study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recommended dose of lapatinib given in combination with standard dose of exemestane in patients with advanced hormone-responsive breast cancer |  | one month after dose selection for each of 3 possible dose levels | 
| proportion of patients free from progression |  | at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment related toxicity |  | every 4 weeks | 
| objective response |  | at 3 and 6 months | 
| time to progression |  | at 12 months | 
| overall survival |  | 18 months | 
| prognostic role of molecular markers and circulating tumor cells |  | at 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced breast cancer, hormone-responsive, metastatic breast cancer