Taxotere and Adriamycin/Cytoxan (AC) Validation in Breast Cancer Patients (TACAC)
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.
|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|
- 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 ]
- 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 ]
|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)|
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.
Other Name: docetaxelDrug: 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.
Other Name: doxorubicinDrug: doxorubicin
AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, every 3 weeks) for 4 cycles before surgery.
Other Name: AC, ADRIAMYCIN/CYTOXAN
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00206518
|Contact: Kristen Otte, BS, CRCemail@example.com|
|Contact: Brenda Reusser, BAfirstname.lastname@example.org|
|United States, Texas|
|Baylor Breast Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Brenda Reusser, BA 713-798-1999 email@example.com|
|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|
|Principal Investigator:||Mothaffar Rimawi, MD||Baylor Breast Center|