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

Breast Cancer Clinical Trial

Official title:

Phase II Safety Study of Docetaxel and Carboplatin in Combination With Trastuzumab and Lapatinib in Early Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00820872
• Other study ID #: NCCTG-N083E
• Secondary ID: NCI-2009-00671CD
• Status: Completed
• Phase: Phase 2
• Start date: February 2009
• Est. completion date: August 15, 2019

Study information

• Verified date: October 2019
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 15, 2019
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab

Drug:
• carboplatin

• docetaxel

• lapatinib ditosylate

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	McFarland Clinic, PC	Ames	Iowa
United States	Hospital District Sixth of Harper County	Anthony	Kansas
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	North Coast Cancer Care - Clyde	Clyde	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Hematology Oncology Center	Elyria	Ohio
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Wayne Hospital	Greenville	Ohio
United States	Northern Montana Hospital	Havre	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Howard Community Hospital	Kokomo	Indiana
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Southwest Medical Center	Liberal	Kansas
United States	Lima Memorial Hospital	Lima	Ohio
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	St. Luke's Hospital	Maumee	Ohio
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients Experiencing Grade 3 or 4 Diarrhea as Measured by NCI CTCAE v3.0		Up to 10 years