Prediction of Response to Neoadjuvant Chemotherapy in Women With Operable Breast Cancer (PT-304)
The objective of this study is to develop a biomarker to predict pathological complete response in women treated with neoadjuvant chemotherapy for breast cancer. Such a biomarker would assist physicians in selecting the most effective chemotherapy for the individual patient.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Prediction of Response to Neoadjuvant Chemotherapy in Women With Operable Breast Cancer|
- Primary clinical endpoint pCR will be a dichotomous outcome variable with two levels: complete response and no complete response. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Secondary clinical endpoint cOR will be an ordinal outcome variable with complete response (CR), partial response (PR), stable disease (SD) and progression disease (PD) four levels. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
Core needle biopsy specimens will be collected and stored in RNAlater® until the time of RNA extraction, using standard procedures. Isolated total RNA will be assayed for gene expression using methods such as TaqMan® RT-PCR technology or Affymetrix or Agilent gene array platforms.
|Study Start Date:||November 2009|
|Study Completion Date:||October 2012|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Other: ChemoFX Assay
The objective of this study is to develop a biomarker to predict pathological complete response in women treated with neoadjuvant chemotherapy for breast cancer. Such a biomarker would assist physicians in selecting the most effective chemotherapy for the individual patient. The anticipated biomarker will take into account clinical factors (such as tumor stage, tumor size, and age), phenotypic characteristics of the tumor (determined by pathological immunohistochemistry and ex vivo ChemoResponse assay), and genotypic characteristics of the tumor and patient (determined by genomic profiling via gene expression analysis of tumor RNA). It is expected that collective consideration of all of these factors will be more predictive of patient response to therapy than any of them alone.
Approximately 224 evaluable subjects will be recruited from approximately 30 US sites. Women with measurable operable invasive breast cancer diagnosed by core needle biopsy will be eligible for this study. Additional tumor specimens will be obtained prior to the start of chemotherapy via core needle biopsies to be used for the ex vivo ChemoResponse Assay and tumor genomic analysis (gene expression), respectively.
All subjects will receive neoadjuvant chemotherapy with one of two standard of care regimens that must consist of the following agents: doxorubicin (A), cyclophosphamide (C), and a taxane (T) such as docetaxel, paclitaxel, or Abraxane (nanoparticle albumin-bound paclitaxel [nab-paclitaxel]); or, docetaxel (T) and cyclophosphamide (C). These must be administered per NCCN guidelines by the treating physician.
Upon completion of chemotherapy treatment, women will undergo lumpectomy, modified radical mastectomy or other surgical procedure determined appropriate by the investigator and at that time will be evaluated for pathological response. At the time of lumpectomy, modified radical mastectomy, or other surgical procedure, additional tumor excess will be sent to Precision Therapeutics, Inc. (Precision) for exploratory analysis if there is no pathologic complete response (pCR), if there are sufficient tumor cells to send, and if the patient agrees to have her excess tumor cells sent to Precision for this purpose.
During the patient's course of participation on the study, the treating physician will remain blinded to the results of the ChemoResponse Assay and genomic analysis. If it is determined there is no pCR at the time of lumpectomy, modified radical mastectomy or other surgical procedure, Precision will make available a subsequent report to the physician containing additional information about chemotherapy drugs other than ACT that could benefit the further treatment decisions for the patient.