Triple Negative Breast CancerNCT01276899
Study to Identify Molecular Mechanisms of Clinical Resistance to Chemotherapy in Triple Negative Breast Cancer Patients
An observational study of Triple Negative Breast Cancer, run by Jewish General Hospital at 8 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Triple Negative Breast Cancer
- What is being tested?
- Needle core biopsies and Needle core biopsies of metastatic lesion
- Type of treatment
- Surgery or procedure
- How many people
- 80 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Sep 2010to Sep 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Neoadjuvant setting
- Histologically confirmed diagnosis of adenocarcinoma of the breast
- Patient candidate for neoadjuvant chemotherapy (taxane-based)
- Triple negative (ERnegative, PRnegative and Her2negative as defined by local standards)
- Normal coagulation profile; including INR/ PTT ≤ 1.5 x ULN.
- ECOG 0,1 or 2
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- Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.
- Able to adhere to the study visit schedule and other protocol requirements.
- Metastatic setting
- Patients with histologically confirmed primary adenocarcinoma of the breast
- Metastatic (stage IV) disease at initial diagnosis or following previous diagnosis of primary breast cancer
- At least one metastatic site accessible for biopsy.
- ER-negative, PgR negative and HER2 negative as per local standards
- Scheduled to receive chemotherapy for triple negative metastatic breast cancer.
- Measurable disease (at least one unidimensionally measurable lesion)
- Normal coagulation profile; including INR/ PTT ≤ 1.5 x ULN.
- ECOG 0,1 or 2
- Life expectancy of 12 or more weeks.
- Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.
- Able to adhere to the study visit schedule and other protocol requirements
Who cannot join
- Neoadjuvant setting
- Positive for ER, PR or Her2 as defined by local standards
- Clinical or radiological evidence of metastatic disease
- Inadequate or unusable tissue as the only tissue available for biopsy
- Other non-malignant systemic disease to preclude treatment with chemotherapy regimen or prevent follow-up
- Diagnosis of inflammatory breast cancer
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- Known infection with HIV or hepatitis
- Metastatic setting
- Patients with ER+, PR+ or HER2+ tumors demonstrated by local standards
- Inadequate or unusable tissue as the only tissue available for biopsy
- Other non-malignant systemic disease to preclude treatment with standard chemotherapy regimen or prevent follow-up
- Abnormal coagulation profile
- The planned concurrent administration of therapies (e.g. palliative radiotherapy) that target metastatic sites accessible for biopsy
- Known infection with HIV or hepatitis
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Canada7 sites
Centre Hospitalier de l'Université de Montréal -- Hotel-Dieu
Montreal, Quebec
Centre Hospitalier de l'Université de Montréal- Notre-Dame
Montreal, Quebec
Hôpital Royal Victoria
Montreal, Quebec
Hôpital Sacré-Coeur
Montreal, Quebec
Jewish General Hospital
Montreal, Quebec
St-Mary's Hospital Center
Montreal, Quebec
Hopital du St-Sacrement
Québec
United States1 site
John H. Stroger, Jr. Hospital of Cook County
Chicago, Illinois
About this study
Official title: 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.
Read the 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.
- Conditions
- Triple Negative Breast Cancer
- Being tested
- Needle core biopsies, Needle core biopsies of metastatic lesion
- Keywords
- Breast Cancer, Triple negative 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
- Medical subject headings
- Triple Negative Breast Neoplasms, Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Needle core biopsiesProcedure or surgery
No investigational products will be administered to subjects as part of this translational research study. Needle core biopsies will be done to collect tumor samples.
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.
Needle core biopsies of metastatic lesionProcedure or surgery
No investigational products will be administered to subjects as part of this translational research study. Needle core biopsies will be done to collect metastasis tumor samples.
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.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant setting | Not described Receives: Procedure: Needle core biopsies | |
| Metastatic setting | Not described Receives: Procedure: Needle core biopsies of metastatic lesion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biomarkers changes in patients that have been exposed to chemotherapy
Measured: 3 years
Secondary outcomes (3)
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.
Measured: 2 years
Study mechanisms of resistance to chemotherapy by profiling for the first time resistant tumors in both the metastatic and advanced primary tumor settings.
Measured: 3 years
Identify biomarkers that will be used as predictors of therapeutic resistance in the tissue and blood of patients with triple negative breast tumors
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2011 (estimated)
- Study startSep 2010
- Primary completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jewish General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Exactis Innovation, Genome Quebec
- Responsible party
- Principal investigator, Mark Basik, Jewish General Hospital
- Investigators
- Mark Basik, MD, Principal investigator, Segal Cancer Centre, Jewish General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01276899
- Sponsor's protocol ID
- Q-CROC-03
- Status last verified
- May 2022
- First submitted
- 12 Jan 2011
- Last updated
- 2 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study to Identify Molecular Mechanisms of Clinical Resistance to Chemotherapy in Triple Negative Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT01276899
- Acronym / sponsor ID
- Q-CROC-03
- Conditions
- Triple Negative Breast Cancer
- Keywords
- Breast Cancer, Triple negative breast cancer, ERnegative, PRnegative and Her2negative, Taxanes, Metastases, Biomarkers, Resistance, Biobanking
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Jewish General HospitalUniversity, hospital or other
- Collaborators
- Exactis Innovation, Genome Quebec
- Study start
- Sep 2010 (actual)
- Primary completion
- Sep 2015 (actual)
- First posted
- 13 Jan 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant setting | – | Procedure: Needle core biopsies |
| Metastatic setting | – | Procedure: Needle core biopsies of metastatic lesion |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (20 listed)
- Neoadjuvant setting
- Histologically confirmed diagnosis of adenocarcinoma of the breast
- Patient candidate for neoadjuvant chemotherapy (taxane-based)
- Triple negative (ERnegative, PRnegative and Her2negative as defined by local standards)
- Normal coagulation profile; including INR/ PTT ≤ 1.5 x ULN.
Key exclusion criteria (14 listed)
- Neoadjuvant setting
- Positive for ER, PR or Her2 as defined by local standards
- Clinical or radiological evidence of metastatic disease
- Inadequate or unusable tissue as the only tissue available for biopsy
- Other non-malignant systemic disease to preclude treatment with chemotherapy regimen or prevent follow-up
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Needle core biopsiesNo investigational products will be administered to subjects as part of this translational research study. Needle core biopsies will be done to collect tumor samples. 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 or surgery | Neoadjuvant setting |
| Needle core biopsies of metastatic lesionNo investigational products will be administered to subjects as part of this translational research study. Needle core biopsies will be done to collect metastasis tumor samples. 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. | Procedure or surgery | Metastatic setting |
Primary outcome
Biomarkers changes in patients that have been exposed to chemotherapy
Time frame: 3 years
3 secondary outcomes
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Basik, MD principal investigator
Segal Cancer Centre, Jewish General Hospital
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Triple Negative Breast Cancer, run by Jewish General Hospital at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biomarkers changes in patients that have been exposed to chemotherapy (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2022.