Adj TC + Herceptin Early Stage Breast Cancer

Breast Cancer Clinical Trial

Official title:

Phase II Trial of Adjuvant TC (Docetaxel/Cyclophosphamide) Plus Trastuzumab in HER2-Positive Early Stage Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00493649
• Other study ID #: 06-038
• Secondary ID: 11270
• Status: Completed
• Phase: Phase 2
• First received: June 27, 2007
• Last updated: May 19, 2014
• Start date: June 2007
• Est. completion date: April 2013

Study information

• Verified date: May 2014
• Source: US Oncology Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 493
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Taxotere
On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.
• Cytoxan
On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.
• Herceptin
On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel 75 mg/m2 IV (over 1 hour), plus cyclophosphamide 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter. Once 4 cycles of TC+H have been received, patients will continue with trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care. The anticipated time to study completion is 5 years.

Locations

Country	Name	City	State
United States	Texas Cancer Center-Abilene (South)	Abilene	Texas
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Texas Oncology, P.A.-Amarillo	Amarillo	Texas
United States	Texas Cancer Center	Arlington	Texas
United States	Texas Oncology Cancer Center	Austin	Texas
United States	Mamie McFaddin Ward Cancer Center	Beaumont	Texas
United States	Texas Oncology, P.A.-Bedford	Bedford	Texas
United States	Birmingham Hematology and Oncology	Birmingham	Alabama
United States	Highline Medical Oncology	Burien	Washington
United States	Hematology Oncology Associates of IL	Chicago	Illinois
United States	Maryland Oncology Hematology, P.A.	Columbia	Maryland
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Methodist Charlton Cancer Ctr.	Dallas	Texas
United States	Texas Cancer Center at Medical City	Dallas	Texas
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Texas Cancer Center	Denton	Texas
United States	Rocky Mountain Cancer Center-Rose	Denver	Colorado
United States	Puget Sound Cancer Center-Edmonds	Edmonds	Washington
United States	El Paso Cancer Treatment Ctr	EL Paso	Texas
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	Fairfax Northern VA Hem-Onc PC	Fairfax	Virginia
United States	Texas Oncology, P.A.	Fort Worth	Texas
United States	Texas Oncology, P.A.	Garland	Texas
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	Texas Oncology, P.A.	Houston	Texas
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Medical Oncology Associates	Kingston	Pennsylvania
United States	Lake Vista Cancer Center	Lewisville	Texas
United States	Longview Cancer Center	Longview	Texas
United States	South Texas Cancer Center-McAllen	McAllen	Texas
United States	Texas Cancer Center of Mesquite	Mesquite	Texas
United States	Allison Cancer Center	Midland	Texas
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	Hematology-Oncology Associates of NNJ, P.A.	Morristown	New Jersey
United States	Florida Cancer Institute	New Port richey	Florida
United States	Ruth Oratz MD	New York	New York
United States	Cancer Care & Hematology Specialists of Chicagoland	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Ocala Oncology Center	Ocala	Florida
United States	Cancer Centers of Florida, P.A.	Ocoee	Florida
United States	Texas Oncology-Odessa	Odessa	Texas
United States	Kansas City Cancer Centers-Southwest	Overland Park	Kansas
United States	Paris Regional Cancer Center	Paris	Texas
United States	Hematology Oncology Associates	Phoenix	Arizona
United States	Cancer Centers of North Carolina	Raleigh	North Carolina
United States	Interlakes Oncology Hematology, PC	Rochester	New York
United States	Onc and Hem Associates of SW VA, Inc.	Salem	Virginia
United States	HOAST-Medical Dr.	San Antonio	Texas
United States	San Antonio Tumor and Blood Clinic	San Antonio	Texas
United States	New Mexico Cancer Care Associates	Santa Fe	New Mexico
United States	Puget Sound Cancer Center-Seattle	Seattle	Washington
United States	Northern AZ Hematology & Oncology Associates	Sedona	Arizona
United States	Texas Cancer Center-Sherman	Sherman	Texas
United States	Cancer Care Northwest-South	Spokane	Washington
United States	Arch Medical Services, Inc.	St. Louis	Missouri
United States	Texas Oncology Cancer Center-Sugar Land	Sugar Land	Texas
United States	Hope Center	Terre Haute	Indiana
United States	Connecticut Oncology & Hematology, LLP	Torrington	Connecticut
United States	Arizona Oncology Associates DBA HOPE	Tucson	Arizona
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists-Vancouver	Vancouver	Washington
United States	Texas Oncology Cancer Care and Research	Waco	Texas
United States	Texas Oncology PA	Webster	Texas
United States	Alliance Hematology Oncology P.A.	Westminster	Maryland
United States	Texoma Cancer Center	Wichita Falls	Texas
United States	Yakima Valley Mem Hosp/North Star Lodge	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
US Oncology Research	Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the DFS at 2 years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC patients treated with TC+H.		To determine the DFS at 2 years	No
Secondary	To determine the overall safety and cardiac safety of 4 cycles of TC+H in HER2+ ESBC patients.		To determine the overall survival at 2 years	Yes