Clinical trial NCT00493649: Adj TC + Herceptin Early Stage Breast Cancer
Official title: Phase II Trial of Adjuvant TC (Docetaxel/Cyclophosphamide) Plus Trastuzumab in HER2-Positive Early Stage Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: US Oncology Research
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2007-06-28
Enrollment: 493
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to find out what effects (good and bad) docetaxel/cyclophosphamide (brand names: Taxotere and Cytoxan, or TC) plus trastuzumab (brand name: Herceptin, or H) has HER2+ breast cancer.


Eligibility criteria: Inclusion Criteria:

A woman will be eligible for inclusion in this study if she meets all of the following criteria:

* Has HER2+ (IHC staining of 3+ \[uniform, intense membrane staining of \>30% of invasive tumor cells\], or a FISH result of .6 HER2 gene copies per nucleus or a FISH ratio \[HER2 gene signals to chromosome 17 signals\] of \>2.2; patients with equivocal FISH ratio results 1.8-2.2 are also eligible if 3+ IHC) (Appendix IX); Stage I, IIA, IIB, or IIIA T1-3N1-3M0 disease. At the discretion of the Treating Physician, patients with 4+ nodes with other factors such as patient choice, older age, preexisting cardiac disease with normal MUGA or ECHO may be enrolled into a separate subgroup.
* Has operable, histologically confirmed, invasive carcinoma of the breast.
* Has known ER and PR status
* Has adequate tumor specimen available for FISH analysis of TOP2A status (See Appendix VII)
* Has had no prior chemotherapy unless it was given \>5 years ago for breast cancer or other cancer
* Has an ECOG Performance Status (PS) 0-1
* Age \>18 to \<70 years old.
* Has laboratory values of: See protocol for specific details
* Has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline phosphatase (ALP) within the ranges shown below. In determining eligibility the more abnormal of the 2 values (AST or ALT) should be used. See protocol for specific details
* Has complete surgical resection of the primary breast tumor: either lumpectomy or mastectomy with sentinel lymph node or axillary dissection.
* It has been \<84 days since the date of definitive surgery, and there is adequate wound healing as determined by the Treating Physician
* Has no evidence of metastatic disease by physical examination and x-ray; appropriate scans as needed by each individual patient (eg, bone scan; abdominal, chest CT; PET or PET/CT; ultrasound; or MRI should indicate no evidence of metastatic disease.
* Has normal cardiac function as evidenced by a LVEF \>50%, but must be within normal limits (WNL) by institutional standard, as determined by multiple gated acquisition (MUGA) scan. An echocardiogram (ECHO). The same modality must be used throughout the study to evaluate LVEF. Ejection fraction (EF) as determined by ECHO must be WNL by institutional standard.
* Has a negative serum pregnancy test within 7 calendar days prior to registration (female patients of childbearing potential \[not surgically sterilized and between menarche and 1 year postmenopause\]).
* If fertile, patient has agreed to use an acceptable method of birth control (barrier contraceptive) to avoid pregnancy for the duration of the study and for a period of 3 months thereafter
* Has signed a Patient Informed Consent Form
* Has signed a Patient Authorization Form

Exclusion Criteria:

A woman will be excluded from this study if she meets any of the following criteria:

* Has any evidence of disease following complete surgical resection of the primary tumor and metastatic workup
* Has Stage IIIB breast cancer (T4 disease; ie, patients with fixed tumors, peau d'orange skin changes, skin ulcerations, or inflammatory changes).
* Has Stage IV breast cancer (M1 disease on TNM staging system)
* Had prior chemotherapy for breast cancer or other cancer within the last 5 years (no neoadjuvant chemotherapy in this study is permitted)
* Has a history of severe hypersensitivity reaction to drugs formulated with polysorbate 80
* Has had a myocardial infarction (MI) within 6 months of trial enrollment, or has New York Heart Association (NYHA) Class II or greater heart failure (see Appendix III), uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic changes
* Has abnormal baseline MUGA (or ECHO) (\<50%, or less than institutional LLN)
* Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy. Adjuvant hormonal therapy, if needed, may be given during radiation therapy and during treatment with trastuzumab after completion of chemotherapy.
* Is receiving concurrent investigational therapy or has received such therapy within the past 30 calendar days
* Has peripheral neuropathy \>Grade 1
* Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious viral (including clinically defined AIDS), bacterial or fungal infection; or history of uncontrolled seizures, or diabetes, or CNS disorders deemed by the Treating Physician to be clinically significant, precluding informed consent
* Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive
* Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the diagnosis or assessment of any of the study drugs
* Is an obese patient to whom the Treating Physician would not be comfortable administering full doses of study drugs as calculated by the BSA. Obese patients will be treated based on actual body weight. Obese patients treated with full doses based on actual BSA are eligible
* Is a pregnant or breastfeeding woman
* Is deemed unable to comply with requirements of study

Primary outcomes:
measure: Disease-free Survival (DFS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H.
timeFrame: 2 years
Secondary outcomes:
measure: Overall Survival (OS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H.
timeFrame: 2 years
measure: DFS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H.
timeFrame: 2 years
measure: OS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H.
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Hematology and Oncology
state: Alabama
city: Phoenix
country: United States
facility: Hematology Oncology Associates
state: Arizona
city: Sedona
country: United States
facility: Northern AZ Hematology & Oncology Associates
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates DBA HOPE
state: Arizona
city: Denver
country: United States
facility: Rocky Mountain Cancer Center-Rose
state: Colorado
city: Torrington
country: United States
facility: Connecticut Oncology & Hematology, LLP
state: Connecticut
city: New Port richey
country: United States
facility: Florida Cancer Institute
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida, P.A.
state: Florida
city: Chicago
country: United States
facility: Hematology Oncology Associates of IL
state: Illinois
city: Niles
country: United States
facility: Cancer Care & Hematology Specialists of Chicagoland
state: Illinois
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Terre Haute
country: United States
facility: Hope Center
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Cancer Centers-Southwest
state: Kansas
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Westminster
country: United States
facility: Alliance Hematology Oncology P.A.
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: St. Louis
country: United States
facility: Arch Medical Services, Inc.
state: Missouri
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Morristown
country: United States
facility: Hematology-Oncology Associates of NNJ, P.A.
state: New Jersey
city: Santa Fe
country: United States
facility: New Mexico Cancer Care Associates
state: New Mexico
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: New York
country: United States
facility: Ruth Oratz MD
state: New York
city: Rochester
country: United States
facility: Interlakes Oncology Hematology, PC
state: New York
city: Raleigh
country: United States
facility: Cancer Centers of North Carolina
state: North Carolina
city: Kettering
country: United States
facility: Greater Dayton Cancer Center
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Center
state: Oregon
city: Kingston
country: United States
facility: Medical Oncology Associates
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Abilene
country: United States
facility: Texas Cancer Center-Abilene (South)
state: Texas
city: Amarillo
country: United States
facility: Texas Oncology, P.A.-Amarillo
state: Texas
city: Arlington
country: United States
facility: Texas Cancer Center
state: Texas
city: Austin
country: United States
facility: Texas Oncology Cancer Center
state: Texas
city: Beaumont
country: United States
facility: Mamie McFaddin Ward Cancer Center
state: Texas
city: Bedford
country: United States
facility: Texas Oncology, P.A.-Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Cancer Center at Medical City
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Dallas
country: United States
facility: Methodist Charlton Cancer Ctr.
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Denton
country: United States
facility: Texas Cancer Center
state: Texas
city: EL Paso
country: United States
facility: El Paso Cancer Treatment Ctr
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Garland
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Houston
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Lewisville
country: United States
facility: Lake Vista Cancer Center
state: Texas
city: Longview
country: United States
facility: Longview Cancer Center
state: Texas
city: McAllen
country: United States
facility: South Texas Cancer Center-McAllen
state: Texas
city: Mesquite
country: United States
facility: Texas Cancer Center of Mesquite
state: Texas
city: Midland
country: United States
facility: Allison Cancer Center
state: Texas
city: Odessa
country: United States
facility: Texas Oncology-Odessa
state: Texas
city: Paris
country: United States
facility: Paris Regional Cancer Center
state: Texas
city: San Antonio
country: United States
facility: San Antonio Tumor and Blood Clinic
state: Texas
city: San Antonio
country: United States
facility: HOAST-Medical Dr.
state: Texas
city: Sherman
country: United States
facility: Texas Cancer Center-Sherman
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology Cancer Center-Sugar Land
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Waco
country: United States
facility: Texas Oncology Cancer Care and Research
state: Texas
city: Webster
country: United States
facility: Texas Oncology PA
state: Texas
city: Wichita Falls
country: United States
facility: Texoma Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Fairfax Northern VA Hem-Onc PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Salem
country: United States
facility: Onc and Hem Associates of SW VA, Inc.
state: Virginia
city: Burien
country: United States
facility: Highline Medical Oncology
state: Washington
city: Edmonds
country: United States
facility: Puget Sound Cancer Center-Edmonds
state: Washington
city: Seattle
country: United States
facility: Puget Sound Cancer Center-Seattle
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest-South
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists-Vancouver
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Mem Hosp/North Star Lodge
state: Washington
Study officials:
affiliation: US Oncology Research
name: Stephen E Jones, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jones SE, Collea R, Paul D, Sedlacek S, Favret AM, Gore I Jr, Lindquist DL, Holmes FA, Allison MAK, Brooks BD, Portillo RM, Vukelja SJ, Steinberg MS, Stokoe C, Crockett MW, Wang Y, Asmar L, Robert NJ, O'Shaughnessy J. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. Lancet Oncol. 2013 Oct;14(11):1121-1128. doi: 10.1016/S1470-2045(13)70384-X. Epub 2013 Sep 3.