Study to Identify Molecular Mechanisms of Clinical Resistance to Chemotherapy in Triple Negative Breast Cancer Patients
Recruitment status was Recruiting
|First Received Date ICMJE||January 12, 2011|
|Last Updated Date||November 28, 2012|
|Start Date ICMJE||September 2010|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Biomarkers changes in patients that have been exposed to chemotherapy [ Time Frame: 3 years ] [ Designated as safety issue: No ]|
|Original Primary Outcome Measures ICMJE
||Identify biomarkers that will be used as predictors of therapeutic resistance in the tissue and blood of patients with triple negative breast tumors. [ Time Frame: 3 years ] [ Designated as safety issue: No ]|
|Change History||Complete list of historical versions of study NCT01276899 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study to Identify Molecular Mechanisms of Clinical Resistance to Chemotherapy in Triple Negative Breast Cancer Patients|
|Official Title ICMJE||Prospective Study to Identify Molecular Mechanisms of Clinical Resistance to Chemotherapy in Triple Negative Breast Cancer Patients|
This is a multicenter translational study to understand therapeutic resistance in patients undergoing standard chemotherapy for triple negative breast cancer.
In the neoadjuvant setting, biopsy tissue samples from primary tumor will be collected and banked before the start of chemotherapy and after the completion of the treatment (post-chemotherapy and at the time of surgery). In the metastatic setting, tissue samples from metastatic lesions will be collected and banked before the start of chemotherapy and at the time of tumor progression. Additionally, blood samples will be drawn before treatment initiation (baseline) and at different time points during treatment. All samples will be stored in the Biological Resource Repository.
Mechanisms of resistance have been studied for many years in various experimental models. However, many drugs that are highly effective in experimental models at overcoming resistance have been either ineffective or marginally active in preliminary clinical studies. Thus after decades of study, most reviews of anti-cancer drug resistance still focus largely on experimental models, which may not reflect resistance in humans. However, recent studies have demonstrated that clinical resistance occurs in primary and metastatic tumors that may have undergone significant molecular evolution due to treatment effects and the selection of clones as recently shown in breast cancer.
Triple negative breast cancer is a subtype that carries a poor prognosis and a high incidence of early metastatic recurrence. Furthermore, no target therapy is efficacious up to now in this subtype. Thus, identification of mechanisms of resistance to available therapies and prediction of tumoral response to various treatments could help in the management of patients affected by this particularly aggressive type of breast cancer.
The goals of this study are two-fold. First, to build a biobank of blood and tissue specimens, prior to starting chemotherapy and at a determined time-point (surgery or progression of disease), from patients undergoing the chemotherapeutic treatments in the neoadjuvant and metastatic settings. Second, to use cutting-edge molecular techniques available in several Quebec research centers, to carefully compare these pre and post treatment samples to identify "molecular factors of resistance". The discovery of these factors will help oncologists in triaging patients to receive the most beneficial therapy by recognizing when not to give particular treatment and will be essential for reducing the potential for harmful side effects and for avoiding the extremely high cost of modern treatments when they can be predicted to be ineffective.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case-Only
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Biospecimen||Retention: Samples With DNA
Tumor samples from the primary breast tumor or metastatic lesions will be obtained by needle core biopsy. In the neoadjuvant setting, samples will be also collected at the time of surgery. To obtain sufficient material for tissue banking, four needle core biopsies will be removed from the same neoplastic lesion. Two of the biospecimens will be snap frozen for phosphoprotein preservation, one will be placed in RNAlater for nucleic acid preservation and the other one will be placed in formalin for FFPE. Additionally, blood samples will be collected at different time points during treatment.
|Sampling Method||Probability Sample|
|Study Population||This study will be conducted in patients with a diagnosis of breast cancer and pathologically identified as triple negative (not expressing estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, and not showing ERBB2 gene amplification) who will be undergoing neoadjuvant treatment or chemotherapy for metastatic disease.|
|Condition ICMJE||Triple Negative Breast Cancer|
|Study Group/Cohort (s)||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||80|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Listed Location Countries ICMJE||United States, Canada|
|Removed Location Countries|
|NCT Number ICMJE||NCT01276899|
|Other Study ID Numbers ICMJE||Q-CROC-03|
|Has Data Monitoring Committee||No|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Mark Basik, Jewish General Hospital|
|Study Sponsor ICMJE||Jewish General Hospital|
|Information Provided By||Jewish General Hospital|
|Verification Date||November 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP