ELBA: Exemestane and Lapatinib in Advanced Breast Cancer (ELBA)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: exemestane; Drug: lapatinib

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Istituto Nazionale dei Tumori , Divisione di Oncologia Medica B
  • Napoli, Italy, 80131
    • Istituto Nazionale dei Tumori, Divisione di Oncologia Medica C
  • Vallo della Lucania, Italy
    • Ospedale S. Luca ASL SA 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Cancer Institute, Naples
• Investigators: Principal Investigator: Francesco Perrone, M.D., Ph.D., NCI Naples, Clinical Trials Office; Principal Investigator: Alessandro Morabito, M.D., NCI Naples; Principal Investigator: Nicola Normanno, M.D., NCI Naples

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Anticipated): October 1, 2011
• Study Completion (Anticipated): March 1, 2012

Study Registration Dates

• First Submitted: October 29, 2009
• First Submitted That Met QC Criteria: October 30, 2009
• First Posted (Estimate): November 1, 2009

Study Record Updates

• Last Update Posted (Estimate): July 13, 2012
• Last Update Submitted That Met QC Criteria: July 12, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: advanced breast cancer; metastatic breast cancer; hormone-responsive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Exemestane; Lapatinib
• Other Study ID Numbers: ELBA; EudraCT number: 2008-007946-67