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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00820872
First received: January 9, 2009
Last updated: June 17, 2012
Last verified: November 2009
  Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving docetaxel together with carboplatin, trastuzumab, and lapatinib may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving docetaxel together with carboplatin, trastuzumab, and lapatinib in treating patients with early stage breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: trastuzumab
Drug: carboplatin
Drug: docetaxel
Drug: lapatinib ditosylate
Procedure: adjuvant therapy
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase II Safety Study of Docetaxel and Carboplatin in Combination With Trastuzumab and Lapatinib in Early Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of patients experiencing grade 3 or 4 diarrhea as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Adverse event profile as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • LVEF [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: February 2009
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • ECOG performance status 0-1
  • Hemoglobin ≥ 10.0 g/dL
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • 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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00820872

  Show 136 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Edith A. Perez, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00820872     History of Changes
Other Study ID Numbers: CDR0000631625, NCCTG-N083E
Study First Received: January 9, 2009
Last Updated: June 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
male breast cancer
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Trastuzumab
Lapatinib
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014