Study to Identify Molecular Mechanisms of Clinical Resistance to Chemotherapy in Triple Negative Breast Cancer Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by Jewish General Hospital
Sponsor:
Collaborators:
Quebec Clinical Research Organization in Cancer
Genome Quebec
Information provided by (Responsible Party):
Mark Basik, Jewish General Hospital
ClinicalTrials.gov Identifier:
NCT01276899
First received: January 12, 2011
Last updated: November 28, 2012
Last verified: November 2012

January 12, 2011
November 28, 2012
September 2010
Not Provided
Biomarkers changes in patients that have been exposed to chemotherapy [ Time Frame: 3 years ] [ Designated as safety issue: No ]
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 ]
Complete list of historical versions of study NCT01276899 on ClinicalTrials.gov Archive Site
  • Create a unique bank of biospecimens from patients with triple negative breast tumors comprising tumor material and plasma collected in a specific and well defined clinical context. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Study mechanisms of resistance to chemotherapy by profiling for the first time resistant tumors in both the metastatic and advanced primary tumor settings. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • 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 ]
  • Create a unique bank of biospecimens from patients with triple negative breast tumors comprising tumor material and plasma collected in a specific and well defined clinical context. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Study mechanisms of resistance to chemotherapy by profiling for the first time resistant tumors in both the metastatic and advanced primary tumor settings. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study to Identify Molecular Mechanisms of Clinical Resistance to Chemotherapy in Triple Negative Breast Cancer Patients
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.

Observational
Observational Model: Case-Only
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

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.

Probability Sample

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.

Triple Negative Breast Cancer
  • Procedure: Needle core biopsies

    No investigational products will be administered to subjects as part of this translational research study.

    A taxane-based regimen will be administered as per the standard of care at each treating institution. Tissue samples from primary tumors will be collected and banked before the start of chemotherapy, after chemotherapy and at the time of surgery. Additionally, blood samples will be drawn before treatment initiation (baseline) and at different time points during treatment and stored in the tissue biobank.

  • Procedure: Needle core biopsies of metastatic lesion

    No investigational products will be administered to subjects as part of this translational research study.

    Chemotherapy will be administered as per the standard of care at each treating institution. Tissue samples from metastatic tumors lesions will be collected and banked before the start of chemotherapy and at the time of progression. Additionally, blood samples will be drawn before treatment initiation (baseline) and at different time points during treatment and stored in the tissue biobank.

  • Neoadjuvant setting
    Intervention: Procedure: Needle core biopsies
  • Metastatic setting
    Intervention: Procedure: Needle core biopsies of metastatic lesion
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
Not Provided
Not Provided

Inclusion Criteria:

Neoadjuvant setting

  1. Histologically confirmed diagnosis of adenocarcinoma of the breast
  2. Patient candidate for neoadjuvant chemotherapy (taxane-based)
  3. Triple negative (ERnegative, PRnegative and Her2negative as defined by local standards)
  4. Normal coagulation profile; including INR/ PTT ≤ 1.5 x ULN.
  5. ECOG 0,1 or 2
  6. Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.
  7. Able to adhere to the study visit schedule and other protocol requirements.

Metastatic setting

  1. Patients with histologically confirmed primary adenocarcinoma of the breast
  2. Metastatic (stage IV) disease at initial diagnosis or following previous diagnosis of primary breast cancer
  3. At least one metastatic site accessible for biopsy.
  4. ER-negative, PgR negative and HER2 negative as per local standards
  5. Scheduled to receive chemotherapy for triple negative metastatic breast cancer.
  6. Measurable disease (at least one unidimensionally measurable lesion)
  7. Normal coagulation profile; including INR/ PTT ≤ 1.5 x ULN.
  8. ECOG 0,1 or 2
  9. Life expectancy of 12 or more weeks.
  10. Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.
  11. Able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

Neoadjuvant setting

  1. Positive for ER, PR or Her2 as defined by local standards
  2. Clinical or radiological evidence of metastatic disease
  3. Inadequate or unusable tissue as the only tissue available for biopsy
  4. Other non-malignant systemic disease to preclude treatment with chemotherapy regimen or prevent follow-up
  5. Diagnosis of inflammatory breast cancer
  6. Known infection with HIV or hepatitis

Metastatic setting

  1. Patients with ER+, PR+ or HER2+ tumors demonstrated by local standards
  2. Inadequate or unusable tissue as the only tissue available for biopsy
  3. Other non-malignant systemic disease to preclude treatment with standard chemotherapy regimen or prevent follow-up
  4. Abnormal coagulation profile
  5. The planned concurrent administration of therapies (e.g. palliative radiotherapy) that target metastatic sites accessible for biopsy
  6. Known infection with HIV or hepatitis
Female
18 Years and older
No
Contact: Zuanel Diaz, PhD 514-340-8222 ext 6129 zdiaz.qcroc@gmail.com
Contact: Adriana Aguilar, PhD 514-340-8222 ext 6589 nanaaguilar@gmail.com
United States,   Canada
 
NCT01276899
Q-CROC-03
No
Mark Basik, Jewish General Hospital
Jewish General Hospital
  • Quebec Clinical Research Organization in Cancer
  • Genome Quebec
Principal Investigator: Mark Basik, MD Segal Cancer Centre, Jewish General Hospital
Jewish General Hospital
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP