Adj TC + Herceptin Early Stage Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
US Oncology Research
ClinicalTrials.gov Identifier:
NCT00493649
First received: June 27, 2007
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Taxotere
Drug: Cytoxan
Drug: Herceptin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Adjuvant TC (Docetaxel/Cyclophosphamide) Plus Trastuzumab in HER2-Positive Early Stage Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by US Oncology Research:

Primary Outcome Measures:
  • To determine the DFS at 2 years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC patients treated with TC+H. [ Time Frame: To determine the DFS at 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the overall safety and cardiac safety of 4 cycles of TC+H in HER2+ ESBC patients. [ Time Frame: To determine the overall survival at 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 493
Study Start Date: June 2007
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TC+H
On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel (Taxotere) 75 mg/m2 IV (over 1 hour), plus cyclophosphamide (Cytoxan) 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab (Herceptin) 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.
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.
Other Name: docetaxel
Drug: 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.
Other Name: cyclophosphamide
Drug: 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.
Other Name: trastuzumab

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00493649

  Show 69 Study Locations
Sponsors and Collaborators
US Oncology Research
Sanofi
Investigators
Principal Investigator: Stephen E Jones, MD US Oncology Research
  More Information

No publications provided

Responsible Party: US Oncology Research
ClinicalTrials.gov Identifier: NCT00493649     History of Changes
Other Study ID Numbers: 06-038, 11270
Study First Received: June 27, 2007
Last Updated: May 19, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Trastuzumab
Cyclophosphamide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
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

ClinicalTrials.gov processed this record on September 30, 2014