Phase I/II Study of Neoadjuvant Lapatinib in Breast Cancer

• Status: Completed
• Trial end date: 2013-07-01
• Target enrollment: 0
• Participant gender: Female

Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, fluorouracil, epirubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving trastuzumab after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of docetaxel and lapatinib when given with or without combination chemotherapy and to see how well they work in treating women with locally advanced, inflammatory, or resectable breast cancer.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborator: GlaxoSmithKline
• Treatments: Docetaxel; Lapatinib; Trastuzumab

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer meeting the following criteria:

• Phase I

• Locally advanced or inflammatory disease, or specified subgroup of large operable disease for whom neoadjuvant chemotherapy is appropriate, defined as any 1 of the following:

• Clinical stage T4a-d, any N (inflammatory breast carcinoma: tumor mass, breast enlargement, oedema and warmth of the skin are often present but not mandatory for the diagnosis)

• Any clinical T, N2 or N3 (ipsilateral supraclavicular nodes)

• cT3cN0,1 any estrogen receptor (ER)

• cT2cN1 any ER

• cT2cN0 ER negative

• Presence of bilateral breast cancer is allowed

• No bone, liver, or other extensive metastases

• Minimal lung, skin, or nodal metastases may be allowed at the discretion of the investigator (phase I only)

• Phase II

• Locally advanced or inflammatory breast cancer, defined as any 1 of the following:

• Clinical T4a-d, any N (inflammatory breast carcinoma: tumor mass, breast enlargement, oedema and warmth of the skin are often present but not mandatory for the diagnosis)

• Any clinical T, N2 or N3 (ipsilateral supraclavicular nodes)

• And M0

• Bilateral breast cancer is allowed provided only 1 side is HER2-positive

• Any large resectable T2 or T3 breast cancers, M0

• HER2-positive disease by immunohistochemistry, fluorescent in situ hybridization, and/or chromogenic in situ hybridization

• No CNS involvement

• Two frozen trucuts for every core biopsy indicated by the translational research study

• Hormone receptor status:

• Estrogen receptor- and/or progesterone receptor-positive or negative tumor

PATIENT CHARACTERISTICS:

• Female

• WHO performance status 0-2

• Hemoglobin > 10.0 g/dL

• Absolute neutrophil count > 1,500/mm^3

• Platelet count > 100,000/mm^3

• Bilirubin < 1.5 times upper limit of normal (ULN)

• AST and ALT < 3 times ULN

• Creatinine < 1.5 times ULN

• No other malignancies within the past 3 years except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix (phase II)

• LVEF normal by MUGA or ECHO

• ECG normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception 2 weeks prior to, during, and for 1 month after completion of study treatment

• No current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease not requiring therapy as per investigator assessment)

• No serious cardiac illness or medical condition within the past 6 months including, but not limited to, any of the following:

• History of documented congestive heart failure

• High-risk uncontrolled arrhythmias

• Angina pectoris requiring antianginal medication

• Clinically significant valvular heart disease

• Evidence of transmural infarction on ECG

• Poorly controlled hypertension, defined as systolic blood pressure (BP) > 180 mm Hg or diastolic BP > 100 mm Hg

• Able to swallow and retain oral medication

• Accessible for repeat dosing and follow up

• No concurrent grapefruit juice

• No active or uncontrolled infection

• No other serious illness

• No malabsorption syndrome

• No other medical condition (i.e., history of chronic alcohol abuse, hepatitis, HIV, and/or cirrhosis)

• No psychological, familial, sociological, or geographical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

• No prior therapy for any cancer, including chemotherapy, radiotherapy, or hormonal therapy for breast cancer (phase I)

• No prior epidermal growth factor receptor- or HER2-targeted therapy or antibody therapy (phase I)

• More than 10 days since prior and no concurrent CYP3A4 inducers or inhibitors

• More than 14 days since prior and no concurrent herbal infusions or dietary supplements

• No antacids 1 hour before or after lapatinib ditosylate administration

• No other concurrent investigational therapy or anticancer therapy

• No concurrent prophylactic antibiotics