Metastatic Breast CancerCOMETI P2NCT01701050
Characterization of Circulating Tumor Cells (CTC) From Patients With Metastatic Breast Cancer Using the CTC-Endocrine Therapy Index
An observational study of Metastatic Breast Cancer, run by Janssen Diagnostics, LLC at 20 sites in 2 countries.
Trial summary
Utilizing CellSearch® technology, the ability to both enumerate and reliably and reproducibly characterize circulating tumor cells (CTC) for tumor markers that predict endocrine sensitivity (estrogen receptor [ER] and Bcl-2) and resistance (HER2 and Ki67) has been demonstrated. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Blood collection
- How many people
- 121 participants
- Where
- 20 sitesin 2 countries
- Study dates
- 1 Apr 2013to 10 Nov 2016
- 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: Female patients 18 years or older with estrogen receptor (ER) positive, HER2 negative, progressive metastatic breast cancer (MBC) after one or more lines of endocrine therapy (ET) who are initiating a new ET will be enrolled into the study. Patients must have immunohistochemistry (IHC) proven ER positive disease, IHC and/or fluorescence in-situ hybridization (FISH) proven HER2 negative disease, and an ECOG performance status of 0-2. Patients with brain metastases only or those who are progressing on fulvestrant are not eligible for the study.
Who may be able to join
- Signed informed consent.
- Women who are 18 years or older.
- Patients must have estrogen receptor (ER) positive, HER2 negative metastatic breast cancer (MBC) with at least one non-irradiated distant site of metastasis.
- ECOG performance status of 0-2.
- Patients must have currently progressive metastatic disease according to RECIST v1.1 criteria, AND
- They have progressed on at least one previous line of endocrine therapy (ET) for their metastatic disease (but are not currently progressing on fulvestrant), OR;
Show all 13Show fewer
- They show evidence of disease progression during or within 12 months of the end of adjuvant ET.
- Patient is about to start a new line of ET for their metastatic disease
- Patient is willing and able to undergo standard of care imaging studies (same imaging/staging modality being used at each evaluation), which are anticipated to be performed prior to the initiation of therapy and subsequently every 3 months.
- Patient agrees to the collection and testing of their blood and is willing and able to provide approximately 40mL blood draw(s) at:
- Baseline (prior to the initiation of new ET), and;
- Subsequently at 1, 2, 3 and 12 months after the initiation of therapy, and/or;
- Time of disease progression.
Who cannot join
- Patients with local regional recurrence only or brain only metastasis.
- Patients who are progressing on current fulvestrant therapy (patients who have had fulvestrant therapy in the past and were subsequently treated with other therapies or those who are starting fulvestrant as their next line of ET are eligible for the study).
- Patients who are or will be taking other unapproved (i.e. not cleared/approved by the FDA) anti-neoplastic therapies concurrently are not eligible (exception: ET with everolimus is acceptable).
- Patients with concomitant malignancies or previous malignancies within the last 5 years, with exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
- Unable to provide informed consent or high risk that patient may not comply with protocol requirements (i.e. due to health and/or participation in other research studies).
Trial locations and contacts
20 sites in 2 countries.
20 sites in 2 countries
United States18 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Dana-Faber Cancer Institute
Boston, Massachusetts, 02215
Waverly Hematology Oncology
Cary, North Carolina, 27518
Texas Oncology - Baylor
Dallas, Texas, 75246
Duke University
Durham, North Carolina, 27710
Florida Cancer Specialists
Fort Myers, Florida, 33905
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, 89074
Texas Oncology
Houston, Texas, 77024
Minnesota Oncology Hematology
Minneapolis, Minnesota, 55404
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
New York Oncology Hematology
New York, New York, 12206
Nebraska Cancer Specialists
Omaha, Nebraska, 68130
Abramson Cancer Center, University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Arizona Oncology Associates
Phoenix, Arizona, 85016
Northwest Cancer Specialists
Portland, Oregon, 97213
Mayo Clinic
Rochester, Minnesota, 55905
Florida Cancer Specialists
St. Petersburg, Florida, 33705
Canada2 sites
Mt. Sinai Hosp., Marvette Koffler Breast Center
Toronto, Ontario, M5G 1X5
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: COMETI Phase 2: Characterization of Circulating Tumor Cells (CTC) From Patients With Metastatic Breast Cancer Using the CTC-Endocrine Therapy Index
Utilizing CellSearch® technology, the ability to both enumerate and reliably and reproducibly characterize circulating tumor cells (CTC) for tumor markers that predict endocrine sensitivity (estrogen receptor [ER] and Bcl-2) and resistance (HER2 and Ki67) has been demonstrated. An algorithm for a CTC-Endocrine Therapy Index (CTC-ETI) has been constructed that can be calculated for each patient using the CTC enumeration and marker results. The primary goal of this study is to determine a CTC-ETI in ER positive, HER2 negative metastatic breast cancer patients before the initiation of a new endocrine therapy for the identification of patients that will progress rapidly.
Read the detailed description
Patients with estrogen receptor (ER) positive metastatic breast cancer (MBC) starting their first line of endocrine therapy (ET) only have a 30-50% chance of receiving clinical benefit. For the other 50-70% of patients, ET is ineffective and these patients should probably be treated with chemotherapy, as is done for ER negative patients. More importantly, in nearly every clinical trial of ET in ER positive, MBC patients, between 15-30% of enrolled patients progress in the first 2-3 months, regardless of whether they are receiving first or later lines of ET. Currently there is no validated method to identify which ER positive MBC patients will be refractory to ET. Therefore, almost all ER positive patients are treated with serial endocrine therapies before switching to chemotherapy. The investigators propose that a subset of these patients would be better served with chemotherapy, in spite of its increased toxicity profile, rather than delaying chemotherapy during a several month trial of ineffective, albeit less toxic, ET.
To try and predict benefit from or resistance to ET, an index (the CTC-ETI) has been created that takes into account the number of CTC (which is prognostic) as well as the phenotype of the CTC, based on the hypothesis that relative levels of ER and Bcl-2 (high=benefit) and HER2 and Ki67 (high=resistance) are predictive of ET responsiveness or resistance. Although the preliminary data demonstrate the ability to detect, enumerate, and characterize CTC utilizing the CellSearch® System, the purpose of the current study is to establish proof of principle that these 4 markers can be used to generate a CTC-ETI which can be performed at baseline from patients enrolled at different centers, and that baseline CTC-ETI predicts relative outcome for patients with ER positive MBC starting a new ET, and can be monitored in such patients during ET. Successful completion of this study will set the stage for a larger, definitive study designed to demonstrate the clinical utility of a "refined" CTC-ETI in patients with ER positive, HER2 negative MBC.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Blood collection
- Keywords
- circulating tumor cells, CTC, metastatic breast cancer, endocrine therapy, hormone therapy
- Medical subject headings
- Breast Neoplasms, Neoplastic Cells, Circulating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood collectionOther
Patients will have blood drawn for circulating tumor cell (CTC) endocrine therapy index (CTC-ETI) calculation at baseline (within 30 days prior to the initiation of endocrine therapy) and then subsequently 1, 2, 3 and up 12 months after the initiation of therapy, or at the time of disease progression, whichever occurs first.
| Study group | Role | What they receive |
|---|---|---|
| Blood collection | Female patients 18 years or older with estrogen receptor (ER) positive, HER2 negative, progressive metastatic breast cancer after one or more lines of endocrine therapy (ET) who are initiating a new ET will be enrolled into the study. Patients must have immunohistochemistry (IHC) proven ER positive disease, IHC and/or fluorescence in-situ hybridization (FISH) proven HER2 negative disease, and an ECOG performance status of 0-2. Patients with brain metastases only or those who are progressing on fulvestrant are not eligible for the study. Receives: Other: Blood collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rapid Disease Progression
Within 30 days prior to the initiation of therapy, chest \& abdomen body imaging (computed tomography [CT], or magnetic resonance imaging [MRI] scanning) plus bone scintigraphic imaging (bone scans or PET scans) or PET-CT scans which encompass both will be performed to identify target and non-target lesions that will be followed with the same imaging techniques 3 months after the initiation of therapy. Objective tumor response will be determined using RECIST v1.1 criteria. Rapid disease progression will be defined as disease progression according to RECIST v1.1 criteria or death due to metastatic breast cancer within 3 months of starting a new ET.
Measured: Within 3 months after initiation of a new line of enrocrine therapy
Secondary outcomes (1)
Progression Free Survival (PFS)
Within 30 days prior to the initiation of of a new line of endocrine therapy (ET), chest \& abdomen body imaging (computed tomography [CT], or magnetic resonance imagine [MRI] scanning) plus bone scintigraphic imaging (bone scans or PET scans) or PET-CT scans which encompass both will be performed to identify target and non-target lesions that will be followed with the same imaging techniques 3 months, 6 months, 9 months, and up to 12 months after the initiation of therapy. Objective tumor response will be determined using RECIST v1.1 criteria. Progression Free Survival (PFS) will be measured as the time from the date of starting ET until the date of first documentation of progressive disease according to RECIST v1.1 criteria or death due to any cause. In the absence of these events, PFS will be censored at the date of the last objective disease assessment (up to a maximum of 12 months after the initiation of ET).
Measured: Up to 12 months after initiation of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2012 (estimated)
- Study start1 Apr 2013
- Primary completion10 Nov 2016
- Study completion10 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Metastatic 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Diagnostics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Daniel F Hayes, M.D., Principal investigator, University of Michigan Rogel Cancer CenterCostanza Paoletti, M.D., Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01701050
- Sponsor's protocol ID
- COMETI-P2-2012
- Acronym
- COMETI P2
- Status last verified
- Mar 2017
- First submitted
- 1 Oct 2012
- Last updated
- 8 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Paoletti C, Connelly MC, Chianese D, et al. Multi-parameter molecular characterization of circulating tumor cells (CTC): Development of a CTC-Endocrine Therapy Index (CTC-ETI). Proc Am Assoc Cancer Res, Abstract 4154, 2011.
Paoletti C, Connelly M, Chianese D, et al. Development of Circulating Tumor Cell-Endocrine Therapy Index in Metastaic Breast Cancer Patients. Cancer Research 71(24 Suppl):451 (Abs. P4-07-16), 2011.
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COMETI Phase 2: Characterization of Circulating Tumor Cells (CTC) From Patients With Metastatic Breast Cancer Using the CTC-Endocrine Therapy Index
- ClinicalTrials.gov ID
- NCT01701050
- Acronym / sponsor ID
- COMETI P2 / COMETI-P2-2012
- Conditions
- Metastatic Breast Cancer
- Keywords
- circulating tumor cells, CTC, metastatic breast cancer, endocrine therapy, hormone therapy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Janssen Diagnostics, LLCIndustry (pharma, biotech, devices)
- Study start
- 1 Apr 2013 (actual)
- Primary completion
- 10 Nov 2016 (actual)
- Study completion
- 10 Nov 2016 (actual)
- First posted
- 4 Oct 2012 (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.
Utilizing CellSearch® technology, the ability to both enumerate and reliably and reproducibly characterize circulating tumor cells (CTC) for tumor markers that predict endocrine sensitivity (estrogen receptor [ER] and Bcl-2) and resistance (HER2 and Ki67) has been demonstrated. An algorithm for a CTC-Endocrine Therapy Index (CTC-ETI) has been constructed that can be calculated for each patient using the CTC enumeration and marker results. The primary goal of this study is to determine a CTC-ETI in ER positive, HER2 negative metastatic breast cancer patients before the initiation of a new endocrine therapy for the identification of patients that will progress rapidly.
Detailed description
Patients with estrogen receptor (ER) positive metastatic breast cancer (MBC) starting their first line of endocrine therapy (ET) only have a 30-50% chance of receiving clinical benefit. For the other 50-70% of patients, ET is ineffective and these patients should probably be treated with chemotherapy, as is done for ER negative patients. More importantly, in nearly every clinical trial of ET in ER positive, MBC patients, between 15-30% of enrolled patients progress in the first 2-3 months, regardless of whether they are receiving first or later lines of ET. Currently there is no validated method to identify which ER positive MBC patients will be refractory to ET. Therefore, almost all ER positive patients are treated with serial endocrine therapies before switching to chemotherapy. The investigators propose that a subset of these patients would be better served with chemotherapy, in spite of its increased toxicity profile, rather than delaying chemotherapy during a several month trial of ineffective, albeit less toxic, ET.
To try and predict benefit from or resistance to ET, an index (the CTC-ETI) has been created that takes into account the number of CTC (which is prognostic) as well as the phenotype of the CTC, based on the hypothesis that relative levels of ER and Bcl-2 (high=benefit) and HER2 and Ki67 (high=resistance) are predictive of ET responsiveness or resistance. Although the preliminary data demonstrate the ability to detect, enumerate, and characterize CTC utilizing the CellSearch® System, the purpose of the current study is to establish proof of principle that these 4 markers can be used to generate a CTC-ETI which can be performed at baseline from patients enrolled at different centers, and that baseline CTC-ETI predicts relative outcome for patients with ER positive MBC starting a new ET, and can be monitored in such patients during ET. Successful completion of this study will set the stage for a larger, definitive study designed to demonstrate the clinical utility of a "refined" CTC-ETI in patients with ER positive, HER2 negative MBC.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Blood collection | – | Other: Blood collectionFemale patients 18 years or older with estrogen receptor (ER) positive, HER2 negative, progressive metastatic breast cancer after one or more lines of endocrine therapy (ET) who are initiating a new ET will be enrolled into the study. Patients must have immunohistochemistry (IHC) proven ER positive disease, IHC and/or fluorescence in-situ hybridization (FISH) proven HER2 negative disease, and an ECOG performance status of 0-2. Patients with brain metastases only or those who are progressing on fulvestrant are not eligible for the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Female patients 18 years or older with estrogen receptor (ER) positive, HER2 negative, progressive metastatic breast cancer (MBC) after one or more lines of endocrine therapy (ET) who are initiating a new ET will be enrolled into the study. Patients must have immunohistochemistry (IHC) proven ER positive disease, IHC and/or fluorescence in-situ hybridization (FISH) proven HER2 negative disease, and an ECOG performance status of 0-2. Patients with brain metastases only or those who are progressing on fulvestrant are not eligible for the study.
Key inclusion criteria (13 listed)
- Signed informed consent.
- Women who are 18 years or older.
- Patients must have estrogen receptor (ER) positive, HER2 negative metastatic breast cancer (MBC) with at least one non-irradiated distant site of metastasis.
- ECOG performance status of 0-2.
- Patients must have currently progressive metastatic disease according to RECIST v1.1 criteria, AND
Key exclusion criteria (5 listed)
- Patients with local regional recurrence only or brain only metastasis.
- Patients who are progressing on current fulvestrant therapy (patients who have had fulvestrant therapy in the past and were subsequently treated with other therapies or those who are starting fulvestrant as their next line of ET are eligible for the study).
- Patients who are or will be taking other unapproved (i.e. not cleared/approved by the FDA) anti-neoplastic therapies concurrently are not eligible (exception: ET with everolimus is acceptable).
- Patients with concomitant malignancies or previous malignancies within the last 5 years, with exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
- Unable to provide informed consent or high risk that patient may not comply with protocol requirements (i.e. due to health and/or participation in other research studies).
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 |
|---|---|---|
| Blood collectionPatients will have blood drawn for circulating tumor cell (CTC) endocrine therapy index (CTC-ETI) calculation at baseline (within 30 days prior to the initiation of endocrine therapy) and then subsequently 1, 2, 3 and up 12 months after the initiation of therapy, or at the time of disease progression, whichever occurs first. | Other | Blood collection |
Primary outcome
Rapid Disease Progression
Time frame: Within 3 months after initiation of a new line of enrocrine therapy
Within 30 days prior to the initiation of therapy, chest \& abdomen body imaging (computed tomography [CT], or magnetic resonance imaging [MRI] scanning) plus bone scintigraphic imaging (bone scans or PET scans) or PET-CT scans which encompass both will be performed to identify target and non-target lesions that will be followed with the same imaging techniques 3 months after the initiation of therapy. Objective tumor response will be determined using RECIST v1.1 criteria. Rapid disease progression will be defined as disease progression according to RECIST v1.1 criteria or death due to metastatic breast cancer within 3 months of starting a new ET.
1 secondary outcome
Progression Free Survival (PFS)
Time frame: Up to 12 months after initiation of therapy
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 8 Mar 2017.
- BackgroundPaoletti C, Connelly MC, Chianese D, et al. Multi-parameter molecular characterization of circulating tumor cells (CTC): Development of a CTC-Endocrine Therapy Index (CTC-ETI). Proc Am Assoc Cancer Res, Abstract 4154, 2011.
- BackgroundPaoletti C, Connelly M, Chianese D, et al. Development of Circulating Tumor Cell-Endocrine Therapy Index in Metastaic Breast Cancer Patients. Cancer Research 71(24 Suppl):451 (Abs. P4-07-16), 2011.
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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.
Daniel F Hayes, M.D. principal investigator
University of Michigan Rogel Cancer Center
Costanza Paoletti, M.D. principal investigator
University of Michigan Rogel Cancer Center
20 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Breast Cancer, run by Janssen Diagnostics, LLC at 20 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 13 inclusion and 5 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 8 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada. 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?
Rapid Disease Progression (time frame: Within 3 months after initiation of a new line of enrocrine therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01701050, which also lists 2 linked publications.
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 8 Mar 2017.