TAC Versus TC for Adjuvant Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
US Oncology Research
ClinicalTrials.gov Identifier:
NCT00493870
First received: June 27, 2007
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

The purpose of this research study is to find out what effects (good and bad) TC or TAC has on early stage HER2- breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: Docetaxel
Drug: Doxorubicin
Drug: Cyclophosphamide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Trial of TC Versus TAC in HER2-Negative Early Stage Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by US Oncology Research:

Primary Outcome Measures:
  • to compare the 3-year DFS of adjuvant TC versus TAC as treatment for early stage HER2-negative breast cancer. [ Time Frame: 3-year ] [ Designated as safety issue: No ]

Enrollment: 1296
Study Start Date: May 2007
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TC
docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2
Drug: Docetaxel
Docetaxel 75 mg/m2 IV over 1 hour on Day 1 followed by cyclophosphamide
Other Name: Taxotere
Drug: Cyclophosphamide
600 mg/m2 IV over 15-30 minutes on Day 1.
Other Name: Cytoxan
Active Comparator: TAC
doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 and docetaxel 75 mg/m2
Drug: Docetaxel
Docetaxel 75 mg/m2 IV over 1 hour on Day 1 followed by cyclophosphamide
Other Name: Taxotere
Drug: Doxorubicin
• Doxorubicin 50 mg/m2 IV push over 5-15 minutes via sidearm through a running IV line on Day 1, followed by cyclophosphamide 500 mg/m2 IV over 15-30 minutes on Day 1, followed by docetaxel 75 mg/m2 IV over 1 hour on Day 1. Administer pegfilgrastim 6 mg SC on Day 2 (or filgrastim 5 mcg/kg SC per standard of care).
Other Name: Adriamycin
Drug: Cyclophosphamide
600 mg/m2 IV over 15-30 minutes on Day 1.
Other Name: Cytoxan

Detailed Description:

Both TAC (docetaxel, doxorubicin, and cyclophosphamide) and TC (docetaxel and cyclophosphamide) are established adjuvant chemotherapy regimens for early stage breast cancer. TAC, however, due to the inclusion of the anthracycline doxorubicin, carries a high risk of hematologic and cardiotoxic adverse effects. Substantial evidence supports the concept that early stage HER2-negative breast cancers will benefit similarly from anthracycline-based adjuvant and non-anthracycline-based chemotherapy.

Further, approximately 0 to 9% of HER2-negative breast cancers have alterations in the TOP2A gene, which may predict for benefit from anthracycline-based chemotherapy.

We hypothesize that 6 cycles of TC versus 6 cycles of TAC will have similar efficacy in the treatment of early stage HER2-negative breast cancer and that TC will have less toxicity. If this hypothesis were upheld and the anthracycline doxorubicin could be eliminated from the regimen while obtaining similar efficacy in this population of patients, it would not only be an important advance in the understanding of the biology of cancer, but it would also be of significant clinical benefit to women with breast cancer.

  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:

  • Age >18 to <70 years old.
  • Has known ER and PR status
  • Has HER2 nonamplified disease, confirmed by FISH
  • Has known menopausal status (see Section 7.3 for criteria)
  • Has operable, histologically confirmed, Stage I, IIA, IIB, or IIIA, IIIB, or IIIC invasive carcinoma of the breast. Bilateral synchronous breast cancer is allowable provided that 1 primary meets the inclusion criteria.
  • Meets 1 of the 3 following criteria:

    • T1-3N1-3M0 if ER positive or negative
    • T2-3N0M0 if ER positive or negative
    • T1N0M0 if ER and PR negative
  • Has complete surgical resection of the primary breast tumor: either lumpectomy or mastectomy with sentinel lymph node biopsy or axillary dissection, with clear margins for both invasive and ductal carcinoma in situ (DCIS)
  • Has had no prior chemotherapy unless >5 years ago
  • Has an ECOG Performance Status (PS) 0-1
  • 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 normal cardiac function as evidenced by a LVEF >50%, but WNL by institutional standard by multiple gated acquisition (MUGA) scan. An echocardiogram (ECHO) may be used if MUGA is not available, but the same modality must be used consistently throughout the study to evaluate LVEF. Ejection fraction as determined by ECHO must be WNL by institutional standard.
  • Has no evidence of metastatic disease outside of breast by physical examination and chest x-ray. Other scans if done as needed by the patient (eg, bone scan; abdominal, chest CT; PET or PET/CT; ultrasound; or MRI should indicate no evidence of metastatic disease
  • Has had baseline bilateral mammography
  • It has been <84 days since the date of definitive surgery (eg, mastectomy or, in the case of a breast-sparing procedure, axillary dissection) with adequate wound healing, as determined by the Treating Physician
  • 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 only) to avoid pregnancy for the duration of the study and for a period of 3 months thereafter
  • Has adequate tumor specimen available for FISH analysis of TOP2A status (See Appendix VI).
  • 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 metastatic disease following surgical resection of the primary tumor including: positive surgical margins, staging work-up, or physical examination suspicious for malignant disease
  • Has 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)
  • Has a history of severe hypersensitivity reaction to drugs formulated with polysorbate 80
  • Has had neoadjuvant chemotherapy for this breast cancer
  • Has ever had a myocardial infarction (MI) or has a history of heart failure, uncontrolled angina, severe uncontrolled arrhythmias, pericardial disease, or electrocardiographic evidence of acute ischemic changes
  • Is receiving concurrent immunotherapy, hormonal therapy (eg, tamoxifen, hormone replacement therapy), or radiation therapy. Must discontinue prior to registering on the study.
  • Is receiving concurrent investigational therapy or has received such therapy within the past 30 calendar days
  • Has peripheral neuropathy >Grade 1
  • Has had a major organ allograft or condition requiring chronic immunosuppression (ie, kidney, liver, lung, heart, bone marrow transplant, or autoimmune diseases). Patients who have received corneal transplants or cadaver skin or bone transplants are eligible.
  • 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, carcinoma in situ of uterine cervix, DCIS, which could affect the diagnosis or assessment of any of the study drugs
  • In 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 pregnant or breastfeeding
  • 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: NCT00493870

  Show 95 Study Locations
Sponsors and Collaborators
US Oncology Research
Sanofi
Investigators
Principal Investigator: Joanne L Blum, MD US Oncology Research
  More Information

No publications provided

Responsible Party: US Oncology Research
ClinicalTrials.gov Identifier: NCT00493870     History of Changes
Other Study ID Numbers: 06090, 11271
Study First Received: June 27, 2007
Last Updated: May 21, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Liposomal doxorubicin
Cyclophosphamide
Doxorubicin
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
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014