Clinical trial NCT01005641: ELBA: Exemestane and Lapatinib in Advanced Breast Cancer
Official title: Phase II Multicentered Study of Exemestane and Lapatinib in Advanced Hormone-responsive Breast Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: advanced breast cancer
hormone-responsive
metastatic breast cancer
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2009-11-01
Enrollment: 0
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: recommended dose of lapatinib given in combination with standard dose of exemestane in patients with advanced hormone-responsive breast cancer
timeFrame: one month after dose selection for each of 3 possible dose levels
measure: proportion of patients free from progression
timeFrame: at 6 months
Secondary outcomes:
measure: Treatment related toxicity
timeFrame: every 4 weeks
measure: objective response
timeFrame: at 3 and 6 months
measure: time to progression
timeFrame: at 12 months
measure: overall survival
timeFrame: 18 months
measure: prognostic role of molecular markers and circulating tumor cells
timeFrame: at 18 months
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori , Divisione di Oncologia Medica B
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori, Divisione di Oncologia Medica C
city: Vallo della Lucania
country: Italy
facility: Ospedale S. Luca ASL SA 3
Study officials:
affiliation: NCI Naples, Division of Medical Oncology C
name: Andrea de Matteis, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: NCI Naples, Clinical Trials Office
name: Francesco Perrone, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: NCI Naples
name: Alessandro Morabito, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: NCI Naples
name: Nicola Normanno, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Campania Luigi Vanvitelli
name: Ciro Gallo, M.D.
role: PRINCIPAL_INVESTIGATOR
References: