Working… Menu

Doxorubicin and Cyclophosphamide Followed By Trastuzumab, Paclitaxel, and Lapatinib in Treating Patients With Early-Stage HER2-Positive Breast Cancer That Has Been Removed By Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00436566
Recruitment Status : Completed
First Posted : February 19, 2007
Results First Posted : November 21, 2012
Last Update Posted : October 8, 2019
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, 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 combination chemotherapy together with trastuzumab and lapatinib after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase II trial is studying the side effects and how well giving doxorubicin together with cyclophosphamide followed by trastuzumab, paclitaxel, and lapatinib works in treating patients with early-stage HER2-positive breast cancer that has been removed by surgery.

Condition or disease Intervention/treatment Phase
Breast Cancer Cardiac Toxicity Biological: trastuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: lapatinib ditosylate Drug: paclitaxel Genetic: gene expression analysis Genetic: reverse transcriptase-polymerase chain reaction Other: fluorophotometry Other: laboratory biomarker analysis Other: mass spectrometry Procedure: adjuvant therapy Procedure: quality-of-life assessment Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 122 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
Official Title: Phase II Study of Cardiac Safety and Tolerability of an Adjuvant Chemotherapy Plus Trastuzumab With Lapatinib in Patients With Resected HER2 + Breast Cancer
Actual Study Start Date : March 16, 2007
Actual Primary Completion Date : April 2009
Actual Study Completion Date : July 22, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Primary Outcome Measures :
  1. Number of Patients With Congestive Heart Failure (CHF) While on Active Treatment [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Adverse Event Profile as Measured by NCI CTCAE v 3.0 [ Time Frame: 5 years ]
    Maximum grade for each type of adverse event will be recorded for each patient.

  2. Cumulative Incidence (CI) of Cardiac Events [ Time Frame: 5 years ]

    Evaluable patients included those completed the AC phase of their treatment regimen; with post AC cardiac evaluation indicates they are eligible to begin treatment with PTL; and those have begun their post-AC therapy.

    Cardiac events: symptomatic congestive heart failure (CHF), cardiac death and other cardiac events (NCI Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3)

  3. Number of Patients Who Experience >= 10 Percent Drop in Left Ventricular Ejection Fraction (LVEF) Between Two Time Points [ Time Frame: 5 years ]
  4. Disease-free Survival (DFS) [ Time Frame: 5 years ]
    DFS was defined as the time from registration to the earliest date of documentation of any local, regional, or distant recurrence of breast cancer (BC); the development of a contralateral BC or second primary other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix, or lobular carcinoma in situ of the breast; or death from any cause without the documentation of one of these events. Participants were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method.

  5. Overall Survival (OS) [ Time Frame: 5 years ]
    OS was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method.

  6. Comparison of Selected Quality-of-life Questionnaires [ Time Frame: 5 years ]
  7. Quality-of-life [ Time Frame: 5 years ]
  8. Incidence of Pulmonary Events [ Time Frame: 5 years ]
    Pulmonary events to be included were grade 3 and higher pulmonary adverse events at least possibly related to study treatment, which occur at any time after post-AC treatment is begun, but prior to documentation of a breast cancer recurrence, contralateral breast cancer, secondary primary cancer, non-pulmonary death, or pulmonary death not related to study treatment.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed diagnosis of early-stage breast cancer

    • HER2 positive by immunohistochemistry (IHC) (3+) or fluorescent in situ hybridization (FISH)

      • Ductal carcinoma in situ (DCIS) components should not be counted in the determination of degree of IHC staining or FISH amplification
  • No locally advanced tumors (i.e., T4) at diagnosis, including the following:

    • Tumors fixed to chest wall
    • Peau d'orange
    • Skin ulcerations or nodules
    • Clinical inflammatory changes (e.g., diffuse brawny cutaneous induration with an erysipeloid edge)
  • Has undergone mastectomy or lumpectomy with axillary node or sentinel node dissection within the past 84 days

    • Patients who have undergone a mastectomy must meet the following criteria:

      • No evidence of gross or microscopic tumor (i.e., invasive DCIS) at the surgical resection margins noted in final surgery or pathology reports

        • Patients with close margins are eligible
      • Radiation therapy is required for 4 or more positive lymph nodes and must be started after completion of chemotherapy
    • Patients who have undergone a lumpectomy with axillary node or sentinel node dissection must meet the following criteria:

      • No evidence of invasive cancer or DCIS at the surgical resection margins
      • No gross residual adenopathy
      • Planning to undergo radiation therapy to the breast with or without regional lymphatics after completion of chemotherapy
  • No active hepatic or biliary disease

    • Patients with liver metastases, stable chronic liver disease, Gilbert's syndrome, or asymptomatic gallstones are eligible
  • Hormone receptor status:

    • Estrogen receptor and progesterone receptor status known


  • Male or female
  • Menopausal status not specified
  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10.0 g/dL
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • LVEF ≥ 50% by MUGA scan or echocardiogram
  • Able to complete questionnaire(s) by themselves or with assistance
  • Able and willing to provide blood and tissue samples
  • No known sensitivity to benzyl alcohol
  • No sensory neuropathy ≥ grade 2
  • No active cardiac disease, including any of the following:

    • Myocardial infarction within the past 6 months
    • Prior or concurrent congestive heart failure
    • Prior or concurrent arrhythmia or cardiac valvular disease requiring medications or that is clinically significant
    • Uncontrolled hypertension, defined as diastolic blood pressure (BP) >100 mm Hg or systolic BP > 200 mm Hg on 2 separate occasions ≥ 14 days apart
    • Clinically significant pericardial effusion
    • Prior or concurrent uncontrolled or symptomatic angina
    • Other cardiac condition that, in the opinion of the treating physician, would put the patient at hazardous risk
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition as lapatinib ditosylate
  • No uncontrolled intercurrent illness including, but not limited to, the following:

    • Ongoing or active infection
    • Psychiatric illness or social situations that would preclude study compliance
  • Able to swallow and retain oral medication

    • No history of gastrointestinal (GI) disease resulting in an inability to take oral medication, including any of the following:

      • Malabsorption syndrome
      • Requirement for IV alimentation
      • Prior surgical procedures affecting absorption
      • Uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment


  • See Disease Characteristics
  • No prior chemotherapy, radiation therapy, immunotherapy, or biotherapy for breast cancer
  • No primary breast radiation therapy as part of breast-conserving treatment
  • No prior anthracycline or taxane therapy for any malignancy
  • No prior epidermal growth factor receptor-targeting therapies (e.g., gefitinib, cetuximab, erlotinib hydrochloride, rituximab, trastuzumab [Herceptin®], lapatinib ditosylate, panitumumab, or nimotuzumab)
  • At least 14 days since prior and no concurrent CYP3A4 inducers, including the following:

    • Rifamycin-class antibiotics (e.g., rifampin, rifabutin, or rifapentine)
    • Anticonvulsants (e.g., phenytoin, carbamazepine, or barbiturates [e.g., phenobarbital])
    • Antiretrovirals (e.g., efavirenz or nevirapine)
    • Glucocorticoids (e.g., oral cortisone, hydrocortisone, prednisone, methylprednisolone, or dexamethasone)

      • Daily oral dexamethasone ≤ 1.5 mg (or equivalent) allowed
    • Modafinil
    • Hypericum perforatum (St. John's wort)
  • At least 7 days since prior and no concurrent CYP3A4 inhibitors, including the following:

    • Antibiotics (e.g., clarithromycin, erythromycin, or troleandomycin)
    • Antifungals (e.g., itraconazole, ketoconazole, fluconazole [> 150 mg daily], or voriconazole)
    • Antiretrovirals and protease inhibitors (e.g., delaviridine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, or lopinavir)
    • Calcium channel blockers (e.g., verapamil or diltiazem)
    • Antidepressants (e.g., nefazodone or fluvoxamine)
    • Gastrointestinal agents (e.g., cimetidine or aprepitant)
    • Grapefruit and grapefruit juice
  • At least 6 months since prior and no concurrent amiodarone
  • No herbal or alternative medicines or supplements ≥ 14 days before, during, and for 30 days after completion of study treatment
  • No concurrent hormonal agents (e.g., birth control pills, ovarian hormonal replacement therapy, or raloxifene)

    • Adjuvant hormonal agents (e.g., tamoxifen, aromatase inhibitors) allowed after completion of chemotherapy as part of treatment for breast cancer
  • No concurrent antiretroviral therapy for HIV-positive patients
  • No concurrent digitalis or beta-blockers for congestive heart failure
  • No concurrent arrhythmia or angina pectoris medication
  • No other concurrent investigational agents or anticancer therapies, including cytotoxic agents or immunotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00436566

Layout table for location information
United States, Minnesota
Mayo Clinic Cancer Research Consortium
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Layout table for investigator information
Study Chair: Edith A. Perez, MD Mayo Clinic
Principal Investigator: Donald W. Northfeld, MD Mayo Clinic
Principal Investigator: James N. Ingle, MD Mayo Clinic in Rochester
Publications of Results:
McCullough A, Dueck A, Chen B, et al.: HER-2 central confirmatory testing using ASCO/CAP guidelines for trastuzumab/lapatinib trial MCCR RC0639. [Abstract] J Clin Oncol 27 (Suppl 15): A-e11527, 2009.
Palmieri FM, Dueck AC, Johnson DB, et al.: Cardiac safety of lapatinib given concurrently with paclitaxel and trastuzumab as part of adjuvant therapy for patients with HER2+ breast cancer: Pilot data from the Mayo Clinic Cancer Research Consortium Trial RC0639. [Abstract] 32nd Annual San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, Texas. A-3086, 2009.
Johnson BS, Dueck AC, Dakhil SR, et al.: Tolerability of lapatinib given concurrently with paclitaxel and trastuzumab as part of adjuvant therapy in patients with resected HER2+ breast cancer: initial safety data from the Mayo Clinic Cancer Research Consortium trial RC0639. [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-2109, 2008.

Layout table for additonal information
Responsible Party: Mayo Clinic Identifier: NCT00436566    
Other Study ID Numbers: CDR0000533793
P30CA015083 ( U.S. NIH Grant/Contract )
RC0639 ( Other Identifier: Mayo Clinic Cancer Center )
06-004049 ( Other Identifier: Mayo Clinic IRB )
First Posted: February 19, 2007    Key Record Dates
Results First Posted: November 21, 2012
Last Update Posted: October 8, 2019
Last Verified: January 2019
Keywords provided by Mayo Clinic:
cardiac toxicity
male breast cancer
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Pathologic Processes
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Radiation Injuries
Wounds and Injuries
Liposomal doxorubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists