Taxotere and Adriamycin/Cytoxan (AC) Validation in Breast Cancer Patients (TACAC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Baylor Breast Care Center
Sponsor:
Collaborator:
Baylor College of Medicine
Information provided by (Responsible Party):
Baylor Breast Care Center
ClinicalTrials.gov Identifier:
NCT00206518
First received: September 14, 2005
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to learn if the biomarker information obtained (learned or received) from the earlier studies can tell us whether or not Taxotere and/or Adriamycin/Cytoxan can cause tumors to become smaller.


Condition Intervention Phase
Breast Cancer
Drug: Taxotere
Drug: Adriamycin/Cytoxan
Drug: docetaxol
Drug: doxorubicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Multicenter Trial of Neoadjuvant Taxotere (T) and Adriamycin/Cytoxan (Ac): A Validation

Resource links provided by NLM:


Further study details as provided by Baylor Breast Care Center:

Primary Outcome Measures:
  • assess clinical tumor response to neoadjuvant chemotherapy (Taxotere and AC) and to validate that clinical response strongly correlates with prospectively-determined regimen-specific gene expression profiles of sensitivity and resistance [ Time Frame: 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • determine time to tumor progression; median overall survival; and document toxicities associated with the chemotherapy regimens [ Time Frame: 10 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 153
Study Start Date: September 2004
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Chemotherapy In Arm A, patients will receive single agent Taxotere (100 mg/m2) every 3 weeks for 4 cycles before surgery. Primary surgery will then be conducted, if operable, following completion of neoadjuvant treatment. This will be followed by standard adjuvant AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, every 3 weeks) for 4 cycles. For patients whose BSA is greater than 2.0 m2, the Adriamycin dosage will be calculated using BSA = 2.0 m2. This is done in order to minimize Adriamycin-induced cardiotoxicity.
Drug: Taxotere
Taxotere
Other Name: docetaxel
Drug: docetaxol
Taxotere (100 mg/m2) every 3 weeks for 4 cycles before surgery.
Other Name: docetaxol, taxotere
Active Comparator: B
In Arm B, patients will receive AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, every 3 weeks) for 4 cycles before surgery. For patients whose BSA is greater than 2.0 m2, the Adriamycin dosage will be calculated using BSA = 2.0 m2. Primary surgery will then be conducted, if operable, following completion of neoadjuvant treatment. This will be followed by 4 cycles of single agent Taxotere (100 mg/m2) every 3 weeks.
Drug: Adriamycin/Cytoxan
Adriamycin/Cytoxan
Other Name: doxorubicin
Drug: doxorubicin
AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, every 3 weeks) for 4 cycles before surgery.
Other Name: AC, ADRIAMYCIN/CYTOXAN

Detailed Description:

Large clinical trials have confirmed the value of systemic adjuvant therapy in decreasing the risk of recurrence and death in patients with early breast cancer. However, the need to identify breast cancer patients who will benefit from adjuvant therapy, while sparing others from the side effects of futile treatment, is spurring research into predictive markers of chemotherapy sensitivity and resistance. In the adjuvant setting, extremely large trials and long follow-up would be required to prospectively validate the predictive value of biomarkers of chemotherapy sensitivity or resistance. In part this is because response is not directly observable. Preoperative chemotherapy for large tumors (>3cm) or inoperable breast cancer is well established and is the standard of care for locally advanced breast cancer. Data from large series of patients have demonstrated that preoperative (neoadjuvant) chemotherapy leads to significant reduction of tumor size (downstaging) and improves both the rate and the cosmetic results of breast- conserving surgery. The degree of response to neoadjuvant therapy has been shown to predict improved overall survival. This is therefore an attractive setting to study predictors of response because tissue is accessible from pre- therapeutic biopsies and tumor response is directly observable.

In an early proof-of-principle pilot study of single agent neoadjuvant docetaxol, we identified a predictive gene expression pattern, and, using leave-one-cross validation, a method of internal validation, we demonstrated that the pattern was likely to accurately discriminate between responders and non-responders (Chang, J.C., et al., Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet, 2003. 362(9381): p. 362-9). A similar pilot study of neoadjuvant AC undertaken by a collaborator in the UK suggests that different profiles will be predictive for AC response.

In order to definitively determine predictive patterns for both regimens (T and AC) using improved technology for RNA preparation and a larger, more comprehensive gene expression array, we undertook a randomized Phase II trial of these two widely used regimens (Protocol H-11624 - A RANDOMIZED MULTICENTER TRIAL OF NEOADJUVANT TAXOTERE AND ADRIAMYCIN/CYTOXAN (AC): A BIOLOGIC CORRELATIVE STUDY). The trial is nearing completion, having recruited more than 90 patients out of an expected 120 patients. To date, the risks associated with this study have been modest, and there have been no unexpected adverse events. The laboratory work is well underway and gives every indication that clinically useful classifiers to predict treatment efficacy will result.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All patients must be female.
  2. Signed informed consent.
  3. Primary breast cancers must be of clinical and/or radiologic size >3 cm, and deemed surgically operable.
  4. Negative serum pregnancy test (bHCG) within 7 days of starting study, if of child-bearing potential.
  5. Adequate bone marrow function:

    • Hematocrit of greater than 30%,
    • total neutrophil count must be >1.5 x 10^9/L and
    • platelets of > 100 x 10^9/L prior to the start of any cycle.
  6. Renal function tests:

    • creatinine within 1.5 times of the institution's upper limit of normal (ULN).
  7. Liver function tests:

    • Total serum bilirubin within ULN, and
    • liver transaminases within 2.5 times ULN, and
    • alkaline phosphatase within 5 times ULN.
  8. Electrocardiogram showing no acute ischemic changes.
  9. Performance status (World Health Organization [WHO] scale) <2.
  10. Age > 18 years.
  11. Patients older than 70 years of age should have left ventricular ejection fraction within ULN by multigated acquisition scan (MUGA) or 2D echocardiogram.

Exclusion Criteria:

  1. Patients with metastatic breast cancer.
  2. Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential.
  3. Women who are lactating or breastfeeding.
  4. Severe underlying chronic illness or disease.
  5. Peripheral neuropathy - grade 2 or greater.
  6. Patients on other investigational drugs while on study will be excluded.
  7. Severe or uncontrolled hypertension, history of congestive heart failure, acute myocardial infarction, or severe coronary arterial disease.
  8. Prior taxane or anthracycline chemotherapy for malignancy.
  9. Patients with a history of severe hypersensitivity reaction to Taxotere or other drugs formulated with polysorbate 80.
  10. No previous or current malignancies at other sites within the last 5 years, with exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.
  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: NCT00206518

Contacts
Contact: Kristen Otte, BS, CRC 713-798-1999 kristen.otte@bcm.edu
Contact: Brenda Reusser, BA 713-798-1929 breusser@bcm.edu

Locations
United States, Texas
Baylor Breast Center Recruiting
Houston, Texas, United States, 77030
Contact: Brenda Reusser, BA    713-798-1999    breusser@breastcenter.tmc.edu   
Sub-Investigator: Garrett Lynch, MD         
Sub-Investigator: C Kent Osborne, MD         
Sub-Investigator: Susan Hislenbeck         
Sub-Investigator: Mothaffar Rimawi, MD         
Sub-Investigator: Julie Nangia, MD         
Sponsors and Collaborators
Baylor Breast Care Center
Baylor College of Medicine
Investigators
Principal Investigator: Mothaffar Rimawi, MD Baylor Breast Center
  More Information

Additional Information:
No publications provided

Responsible Party: Baylor Breast Care Center
ClinicalTrials.gov Identifier: NCT00206518     History of Changes
Other Study ID Numbers: H 16039
Study First Received: September 14, 2005
Last Updated: July 22, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Baylor Breast Care Center:
Breast
Cancer
Taxotere
AC
Validation
Neoadjuvant

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Docetaxel
Doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on July 28, 2014