A Randomized, Double-blind, Multicenter, Placebo-controlled Study of Adjuvant Lapatinib in Women with Early-Stage ErbB2 Overexpressing Breast Cancer

• Conditions: Women with early-stage ErbB2-overexpressing breast cancer. Eligible women must have had an initial diagnosis of histologically or cytologically confirmed invasive breast cancer (Stage I through Stage IIIb) with ErbB2 overexpression defined as 3+ by immunohistochemisty (IHC) or c-erbB2 gene amplification by fluorescence in-situ hybridization (FISH).

• Registration Number: EUCTR2005-005186-10-LV
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-08-23
• Last Update Posted: 18 February 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 3000

Inclusion Criteria

•Histologically or cytologically confirmed ErbB2-overexpressing invasive carcinoma (Tx or T1-4) of the breast at initial diagnosis and undergone adequate excision of tumour;
•Women with synchronous bilateral invasive breast cancer or synchronous DCIS of either the contralateral or ipsilateral breast at the time of the initial diagnosis are also eligible; prior endocrine therapy as treatment for or as primary prevention of DCIS is allowed.
•Completed all primary adjuvant chemotherapy regimens prior to study enrolment. However, adjuvant endocrine therapy and radiotherapy may continue. For women who received an anthracycline-based adjuvant regimen, the interval between the completion of this therapy and study entry must be at least 4 weeks and all therapy-related toxicity must be resolved.
•Women who have not received trastuzumab in the adjuvant setting, but are eligible for such treatment, are allowed to participate in this study provided the physician and patient have considered the treatment and decided not to initiate therapy with trastuzumab, for practical reasons. Clear documentation of such decision must appear in the Electronic Case Report Form (eCRF);
•Have clinical and radiologic assessments that are negative for local or regional recurrence of disease or metastatic disease at the time of study entry:
•Must have had an analysis of both ER and progesterone receptor (PgR) on the primary tumour prior to study entry;
•Have undergone either total mastectomy OR lumpectomy;
•Must have received a prior adjuvant chemotherapy regimen containing either an anthracycline or a taxane; or any cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen;
•May continue to receive endocrine therapy, including tamoxifen or an aromatase inhibitor, while taking study medication, if endocrine therapy was initiated as either adjuvant therapy for treatment of the initial diagnosis of invasive breast cancer or for ovarian function suppression;
•May have received prior radiotherapy as treatment for primary tumour.
•May continue to receive radiotherapy while taking study medication, if radiotherapy was initiated as adjuvant therapy for treatment of the initial diagnosis of invasive breast cancer;
•May continue to receive bisphosphonates only for treatment of documented osteoporosis, but not as treatment or prophylaxis of bone metastases;
•Have not received prior therapy with an ErbB1 and/or ErbB2 inhibitor;
•Have a cardiac ejection fraction within institutional range of normal measured by either ECHO or MUGA scans.
•Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 .
•Women with a history of non-breast malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence. Women with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical carcinoma in situ, melanoma in situ, and basal cell or squamous cell carcinoma of the skin;
•Are able to swallow and retain oral medication;
•Have an archived tumour tissue samples available for biomarker analysis.
•Able to complete all screening assessments as outlined in the protocol;
•Have adequate organ function
•Have signed the informed consent form (ICF);
•Are aged >= 18 years with any menopausal status;
•Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are post- meno

Exclusion Criteria

Women will not be eligible for inclusion in this study if any of the following criteria apply:
1.Have clinical and radiologic evidence of local or regional recurrence of disease or metastatic disease at the time of study entry;
2.Had metachronous invasive breast cancer (breast cancers diagnosed at different times);
3.Have a prior history of other breast cancer malignancies, including DCIS;
4.Are unable to provide archived tumor tissue samples for assay;
5.Had prior therapy with an ErbB1 and/or ErbB2 inhibitor;
6.Receive concurrent anti-cancer therapy (chemotherapy, immunotherapy, and biologic therapy) while taking study medication;
7.Have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
8.Have malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Women with ulcerative colitis are also excluded;
9.Have a concurrent disease or condition that would make the woman inappropriate for study participation, or any serious medical disorder that would interfere with the woman's safety;
10.Have an active or uncontrolled infection;
11.Have dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
12.Have a known history of uncontrolled or symptomatic angina, arrhythmias, or CHF;
13.Are pregnant or breastfeeding;
14.Receive concurrent treatment with an investigational agent or participate in another clinical trial;
15.Receive concurrent treatment with prohibited medications (refer to Section 8.2 for details on prohibited medications);
16.Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication;
17.Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients;
18.In France, subjects are neither affiliated with nor a beneficiary of a social security category.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified