Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Docetaxel, Carboplatin, Trastuzumab, and Lapatinib in Treating Patients With Early Stage Breast Cancer

Basic Trial Information

Objectives

Primary

1. Determine the safety and tolerability (including the rate of diarrhea) of adjuvant therapy comprising docetaxel, carboplatin, trastuzumab (Herceptin®), and lapatinib ditosylate in patients with early-stage breast cancer.

Secondary

1. Evaluate the adverse event profile of this regimen in these patients.
2. Evaluate LVEF in patients receiving this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed primary invasive adenocarcinoma of the breast fulfilling the following criteria:
  • Nonmetastatic disease
  • Operable and adequately excised
    • Patients with nonresectable deep margin invasion are eligible provided they have had or will receive radiotherapy to the region
    • Patients with histologically documented infiltration of the skin (pT4) are eligible provided they have undergone or will receive radiotherapy encompassing the tumor bed
  • Node-positive OR -negative and determined eligible to receive adjuvant trastuzumab (Herceptin®)
• No positive or suspicious internal mammary nodes by SNS that have not been or will not be irradiated
• No supraclavicular lymph node involvement (confirmed by fine needle aspiration or biopsy)
• Over expression and/or amplification of HER2 in the invasive component of the primary tumor, according to one of the following:
  • 3+ over-expression by IHC (> 30% of invasive tumor cells)
  • 2+ or 3+ (in 30% or less neoplastic cells) over-expression by IHC AND in situ hybridization (FISH/CISH) test demonstrating HER2 gene amplification
  • HER2 gene amplification by FISH/CISH (> 6 HER2 gene copies per nucleus, or a FISH ratio [HER2 gene copies to chromosome 17 signals] of > 2.2.)
    • Negative or equivocal overall result (FISH test ratio of < 2.2, < 6.0 HER2-gene copies per nucleus) and staining scores of 0, 1+, 2+, or 3+ (in 30% or less neoplastic cells) by IHC not allowed
• Hormone receptor status known (estrogen receptor with or without progesterone receptor)

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior mediastinal irradiation except internal mammary-node irradiation for the present breast cancer
• No prior anti-HER2 therapy for any reason
• No prior biologic or immunotherapy for breast cancer
• No prior resection of the stomach or small bowel
• No other concurrent anticancer therapy including chemotherapeutic agents, biologic agents, or radiotherapy
• No concurrent anticancer treatment in another investigational trial with hormone therapy or immunotherapy unless approved by the study chair
• No concurrent CYP3A4 inhibitors or inducers
• No concurrent epoetin alfa, including darbepoetin alfa
• No concurrent oprelvekin

Patient Characteristics:

• Menopausal status not specified
• ECOG performance status 0-1
• Hemoglobin ≥ 10.0 g/dL
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Serum creatinine ≤ 2.0 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Bilirubin ≤ 1.5 times ULN (≤ 2.0 times ULN if known Gilbert syndrome)
• Baseline LVEF ≥ 50% measured by ECHO or MUGA scan
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious cardiac illness or medical condition including, but not limited to, any of the following:
  • History of documented congestive heart failure (any NYHA class) or systolic dysfunction (LVEF < 50%)
  • High-risk uncontrolled arrhythmias (e.g., ventricular tachycardia, high-grade atrioventricular-block [second degree or higher], or supraventricular arrhythmias that are not adequately rate-controlled)
  • Angina pectoris requiring antianginal medication
  • Clinically significant valvular heart disease
  • Evidence of transmural infarction on ECG
  • Poorly controlled hypertension (any reading of systolic BP > 180 mm Hg or diastolic BP > 100 mm Hg)
• No other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions or illness
• None of the following:
  • Ulcerative colitis
  • Malabsorption syndrome
  • Any disease significantly affecting gastrointestinal function
  • Inability to swallow oral medication

Expected Enrollment

Outcomes

Proportion of patients experiencing grade 3 or 4 diarrhea as measured by NCI CTCAE v3.0

Adverse event profile as measured by NCI CTCAE v3.0
LVEF

Outline

Patients receive docetaxel IV over 60 minutes and carboplatin IV over 30 minutes on day 1, trastuzumab (Herceptin®) IV over 30-90 minutes on days 1, 8, and 15, and oral lapatinib ditosylate on days 1-21 (TCHL). Treatment with TCHL repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV over 30-90 minutes on day 1 and oral lapatinib ditosylate on days 1-21 (days 1-7 of course 12 only) (LT). Treatment with LT repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity..

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 8 years.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Edith Perez, MD, Protocol chair		Ph: 507-284-1159 Email: perez.edith@mayo.edu

Registry Information
Official Title		Phase II Safety Study of Docetaxel and Carboplatin in Combination with Trastuzumab and Lapatinib in Early Breast Cancer
Trial Start Date		2009-02-20
Trial Completion Date		2009-04-02 (estimated)
Registered in ClinicalTrials.gov		NCT00820872
Date Submitted to PDQ		2008-12-30
Information Last Verified		2009-11-13
NCI Grant/Contract Number		CA25224

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