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

NCT00436566 | Completed Phase 2 Results DMC

• 4 other identifiers: CDR0000533793P30CA015083RC063906-004049
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Cardiac Toxicity

Keywords

cardiac toxicity; male breast cancer; stage I breast cancer; stage II breast cancer; stage IIIA breast cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Congestive Heart Failure (CHF) While on Active Treatment

  6 months

Secondary Outcomes (8)

• Adverse Event Profile as Measured by NCI CTCAE v 3.0

  5 years

• Cumulative Incidence (CI) of Cardiac Events

  5 years

• Number of Patients Who Experience >= 10 Percent Drop in Left Ventricular Ejection Fraction (LVEF)

  5 years

• Percentage of Participants With Disease-Free Survival (DFS)

  5 years

• Percentage of Participants With Overall Survival (OS)

  5 years

Interventions

trastuzumab BIOLOGICAL

cyclophosphamide DRUG

doxorubicin hydrochloride DRUG

lapatinib ditosylate DRUG

paclitaxel DRUG

gene expression analysis GENETIC

reverse transcriptase-polymerase chain reaction GENETIC

fluorophotometry OTHER

laboratory biomarker analysis OTHER

mass spectrometry OTHER

adjuvant therapy PROCEDURE

quality-of-life assessment PROCEDURE

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * 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 PATIENT CHARACTERISTICS: * 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 PRIOR CONCURRENT THERAPY: * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic Cancer Research Consortium

Rochester, Minnesota, 55905, United States

Location

Related Publications (3)

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Breast Neoplasms; Cardiotoxicity; Breast Neoplasms, Male

Interventions

Trastuzumab; Cyclophosphamide; Doxorubicin; Lapatinib; Paclitaxel; Gene Expression Profiling; Reverse Transcriptase Polymerase Chain Reaction; Fluorophotometry; Mass Spectrometry; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Genetic Techniques; Investigative Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Diagnostic Techniques, Ophthalmological; Diagnostic Techniques and Procedures; Diagnosis; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Combined Modality Therapy; Therapeutics; Drug Therapy

Results Point of Contact

• Title: Dr. Edith A. Perez
• Organization: Mayo Clinic

perez.edith@mayo.edu

507-266-0800

Study Officials

• Edith A. Perez, MD

  Mayo Clinic

  STUDY CHAIR

• Donald W. Northfeld, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• James N. Ingle, MD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 19, 2007
• Study Start: March 16, 2007
• Primary Completion: April 1, 2009
• Study Completion: July 22, 2019
• Last Updated: August 5, 2022
• Results First Posted: November 21, 2012

Record last verified: 2019-01

Locations

US (1)