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
  Purpose

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.


Condition Intervention
Triple Negative Breast Cancer
Procedure: Needle core biopsies
Procedure: Needle core biopsies of metastatic lesion

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Prospective Study to Identify Molecular Mechanisms of Clinical Resistance to Chemotherapy in Triple Negative Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by Jewish General Hospital:

Primary Outcome Measures:
  • Biomarkers changes in patients that have been exposed to chemotherapy [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

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.


Estimated Enrollment: 80
Study Start Date: September 2010
Groups/Cohorts Assigned Interventions
Neoadjuvant setting 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.

Metastatic setting 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.


Detailed Description:

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.

  Eligibility

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

Criteria

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
  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: NCT01276899

Contacts
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

Locations
United States, Illinois
John H. Stroger, Jr. Hospital of Cook County Recruiting
Chicago, Illinois, United States
Contact: Wendy A Rogowski    312-864-5204    wendyarogowski@hotmail.com   
Sub-Investigator: Elizabeth Marcus, MD         
Canada, Quebec
Jewish General Hospital Recruiting
Montreal, Quebec, Canada
Contact: Rosa Christodoulopoulos, PhD    514-340-8222 ext 6823    rchristodoulopoulos@jgh.mcgill.ca   
Contact: Shirin Kazemi, PhD    514-340-8222 ext 4302    skazemi@jgh.mcgill.ca   
Principal Investigator: Mark Basik, MD         
Centre Hospitalier de l'Université de Montréal -- Hotel-Dieu Recruiting
Montreal, Quebec, Canada
Contact: Christine Ghorayeb, MSc    514-890-8000 ext 14944    christine.ghorayeb.chum@ssss.gouv.qc.ca   
Sub-Investigator: André Robidoux, MD         
Centre Hospitalier de l'Université de Montréal- Notre-Dame Recruiting
Montreal, Quebec, Canada
Contact: Isabelle Nadeau    514-890-8000 ext 23896    isabelle.nadeau.chum@ssss.gouv.qc.ca   
Sub-Investigator: Jean-Pierre Ayoub, MD         
St-Mary`s Hospital Center Recruiting
Montreal, Quebec, Canada
Contact: Melania Cartillone    514-345-3511 ext 3981    melania.cartillone.chsm@ssss.gouv.qc.ca   
Sub-Investigator: Richard Dalfen, MD         
Hôpital Sacré-Coeur Recruiting
Montreal, Quebec, Canada
Contact: Karine Chaussé, Inf    514 338-2222 ext 2818    karine.chausse@crhsc.rtss.qc.ca   
Sub-Investigator: Josée Anne Roy, MD         
Hôpital Royal Victoria Recruiting
Montreal, Quebec, Canada
Contact: Ramy Saleh, MD    514-934-1934 ext 36897    ramy.saleh2@mail.mcgill.ca   
Sub-Investigator: Catalin Mihalcioiu, MD         
Canada
Hopital du St-Sacrement Recruiting
Quebec, Canada
Contact: Eric Vachon, PhD    418-682-7511 ext 4728    eric.vachon.cha@ssss.gouv.qc.ca   
Sub-Investigator: Christine Desbiens, MD         
Sponsors and Collaborators
Jewish General Hospital
Quebec Clinical Research Organization in Cancer
Genome Quebec
Investigators
Principal Investigator: Mark Basik, MD Segal Cancer Centre, Jewish General Hospital
  More Information

No publications provided

Responsible Party: Mark Basik, Principal Investigator, Jewish General Hospital
ClinicalTrials.gov Identifier: NCT01276899     History of Changes
Other Study ID Numbers: Q-CROC-03
Study First Received: January 12, 2011
Last Updated: November 28, 2012
Health Authority: Canada: Jewish General Hospital Institutional Review Board

Keywords provided by Jewish General Hospital:
Triple negative breast cancer
Breast Cancer
ERnegative, PRnegative and Her2negative
Taxanes
Metastases
Biomarkers
Resistance
Biobanking
Breast cancer with unresectable metastases to the liver
Breast cancer with unresectable metastases to the skin
Breast cancer with unresectable metastases to the lymph node
Neoadjuvant chemotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on July 29, 2014