Metastatic Colorectal CancerBRECOLNCT01733628
Evaluation of Hypertension as a Predictor of Efficacy Bevacizumab in Metastatic Breast Cancer and Colorectal Cancer
An observational study of Metastatic Colorectal Cancer and Metastatic Breast Cancer, run by Spanish Breast Cancer Research Group at 10 sites in Spain.
Trial summary
This is a multicenter, post-authorization observational with prospective follow-up (EPA-SP) study. Will be involved 137 metastatic breast cancer patients or metastatic colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer, Metastatic Breast Cancer
- How many people
- 143 participants
- Where
- 10 sitesSpain
- Study dates
- 23 Oct 2012to 19 Dec 2017
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with metastatic (disseminated at the time of diagnosis) breast cancer or colorectal cancer, treated with bevacizumab.
Who may be able to join
- May only participate in the study patients (women and men) who meet all the following criteria:
- MCC or MBC patients with chemotherapy and bevacizumab established indication. The first line systemic treatment planned for patients with MCC should be based in combination chemotherapy (oxaliplatin / irinotecan plus fluoropyrimidine) associated with bevacizumab. The first line systemic treatment planned for MBC patients should be based on a combination of paclitaxel or capecitabine plus bevacizumab.
- Presence of measurable or evaluable disease according to RECIST 1.1, for the evaluation of the response to treatment.
- Equal or more than 18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Signed written informed consent.
- Women of childbearing potential must have a negative pregnancy test in serum or urine conducted in the 7 days prior to the administration of chemotherapeutic treatment assigned by your doctor, and accept the use of double barrier contraception during the study (Note : Patients who are not of childbearing age may participate without using contraceptives. Women who are of childbearing age are those who: 1) have reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) within postmenopausal interval as determined by the laboratory, or 12 months of spontaneous amenorrhea), 2) have undergone bilateral oophorectomy with or without hysterectomy 6 weeks before, or 3) have undergone bilateral tubal ligation). Men also should use an adequate contraception method.
Who cannot join
- Patients meeting any of the following circumstances will be excluded from the study:
- Have received prior systemic anticancer therapy with chemotherapy for advanced disease or prior treatment with bevacizumab.
- Treatment with an investigational agent or biological agent within 30 days prior to inclusion in the study.
- Contraindications to treatment with chemotherapy and bevacizumab according to summary products characteristics.
- Background or current history (within five years before the start of treatment) of other malignancies, except for colorectal carcinoma and breast cancer (patients with basal cell carcinoma or squamous cell skin or cervical carcinoma in situ treated curative may be included in the study).
- Life expectancy less than 3 months.
- Patients who are pregnant or breastfeeding.
- Patients with an inadequate organ function (bone marrow, kidney and liver)
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Spain10 sites
Complejo Hospitalario Universitario A Coruña
A Coruña, 15006
Hospital General Universitario de Alicante
Alicante
Complejo Hospitalario Universitario Reina Sofía
Córdoba
Hospital General Universitario de Elche
Elche, Alicante
Complejo Hospitalario de Jaén
Jaén
Centro Oncológico MD Anderson
Madrid
Hospital General Universitario Gregorio Marañón
Madrid
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario La Fe
Valencia
Hospital Universitario Miguel Servet
Zaragoza
About this study
Official title: Evaluation Study of Hypertension as a Predictor of Efficacy Bevacizumab (BV) in Combination With Chemotherapy (CT) in Metastatic Colorectal Cancer (MCC) and Metastatic Breast Cancer (MBC).
This is a multicenter, post-authorization observational with prospective follow-up (EPA-SP) study. Will be involved 137 metastatic breast cancer patients or metastatic colorectal cancer. The hypertension will be evaluated as a predictor of efficacy of bevacizumab associated with chemotherapy, in terms of progression-free survival (PFS) (Main endpoint).
The duration of the study will be approximately 42 months.
Read the detailed description
Hypertension (HT) is the most common side effect seen in trials of bevacizumab in combination with chemotherapy. Based on the hypothesis that the development of hypertension during treatment would be an indicative of the successful blockade of the Vascular Endothelial Growth Factor (VEGF) pathway, different studies have explored retrospectively the relationship between hypertension and the results of treatment with bevacizumab.
This study aims to demonstrate the association between hypertension (diagnosed optimally) with efficacy to treatment with bevacizumab prospectively and secondly verify if blood pressure measures taken at home are a reflection of a diagnosis of hypertension.
Also have been explored different molecular markers involved in the pathway of VEGF which might be used as predictors of response. Therefore, this study includes the collection of blood samples (serum or plasma) and tumor tissue of patients included in this study, with the aim of exploring biomarkers that correlate with treatment efficacy and toxicity.
The diagnosis of hypertension (HT) will be performed using a Holter recording, and standard blood pressure footage will be collected during the first three cycles of treatment given the Common Toxicity Criteria of the National Cancer Institute-NCI CTCAE version 4.0 and the guidelines of the European Society of Cardiology and Hypertension, 2007.
Will be collected a sample of primary tumor and blood for patients who previously have consented it. Samples will be sent to a central laboratory for analysis of biomarkers.
An interim analysis will be conducted to assess the true incidence of hypertension. Based on this analysis, will be evaluated the need to recalculate the sample size.
At the end of the study, will be performed an analysis of correlation of data measured by standard BP (Blood Pressure) and Holter recording footage with the PFS. Moreover will be determined in serum, plasma and tumor tissue and certain biomarkers to correlate with efficacy to treatment with bevacizumab.
- Keywords
- Hypertension, Bevacizumab Response Predictors, Metastatic Breast Cancer, Metastatic Colon Cancer
- Medical subject headings
- Colorectal Neoplasms, Breast Neoplasms, Hypertension, Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab + Chemotherapy | Patients who received the addition of Bevacizumab (BV) every 2-3 weeks to Chemotherapy (CT) with either oxaliplatin or irinotecan plus fluoropyrimidines in patients with Metastatic Colorectal Cancer (MCRC), either paclitaxel or capecitabine in patients with Metastatic Breast Cancer (MBC), as first-line therapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With or Without Blood Pressure Increase as a Predictor of Progression Free Survival (PFS)
The incidence of hypertension was studied during treatment with bevacizumab combined with chemotherapy. A Cox regression analysis was performed, entering as a dependent variable the PFS and as independent variable the Arterial Hypertension (AHT) (yes/no). AHT is introduced in the model of Cox as a time-dependent variable since its situation can change as length of the study. The date on which the AHT changes (passes from normotensive to hypertensive).
Measured: Up to 3 years
Progression Free Survival (PFS)
The PFS is the time from the patient receiving the first dose of chemotherapy for advanced disease to the date of progression, the administration of a new antineoplastic treatment that does not contain bevacizumab or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Up to 3 years
Secondary outcomes (2)
Number of Participants With "White Coat" AHT While at Home
The incidence of "white coat" arterial hypertension (AHT) was evaluated comparing each of the measurements in medical attention (in a doctor office) with the measurement that was made at home (without a doctor).
White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.
Measured: Cycle 1, cycle 2, and cycle 3, up to 9 weeks
Number of Participants With "White Coat" AHT With 24 Hours Ambulatory BP Measure
The incidence of "white coat" arterial hypertension (AHT) was evaluated comparing each of the measurements with the measurement that was made in the hospital. Ambulatory Blood Pressure Monitoring (ABPM) is when the blood pressure is being measured as patient moves around, living her normal daily life.
White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.
Measured: Baseline, cycle 1, cycle 2, and cycle 3, up to 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2012 (estimated)
- Study start23 Oct 2012
- Primary completion19 Dec 2017
- Study completion19 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal 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
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spanish Breast Cancer Research Group
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Farma, S.A
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Hospital General Universitario de Elche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01733628
- Sponsor's protocol ID
- GEICAM/2011-04
- Other IDs
- GEI-BEV-2011-02
- Acronym
- BRECOL
- Status last verified
- Dec 2019
- First submitted
- 20 Nov 2012
- Last updated
- 4 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Rodriguez-Lescure A, Gallego J, Garcia-Alfonso P, Massuti B, Marquez R, Calvo L, Sanchez-Rovira P, Anton A, Chacon JI, Ciruelos E, Ponce JJ, Santaballa A, Valladares-Ayerbes M, Duenas MR, Alonso V, Aparicio J, Encinas S, Robles L, Escudero MJ, Caballero R, Bezares S, Garcia-Ortiz MV, Morales-Ruiz T, de la Haba-Rodriguez J. Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study. Clin Transl Oncol. 2024 Aug;26(8):1896-1907. doi: 10.1007/s12094-024-03411-w. Epub 2024 Apr 5.
PubMed 38578537
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation Study of Hypertension as a Predictor of Efficacy Bevacizumab (BV) in Combination With Chemotherapy (CT) in Metastatic Colorectal Cancer (MCC) and Metastatic Breast Cancer (MBC).
- ClinicalTrials.gov ID
- NCT01733628
- Acronym / sponsor ID
- BRECOL / GEICAM/2011-04
- Keywords
- Hypertension, Bevacizumab Response Predictors, Metastatic Breast Cancer, Metastatic Colon Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- Spanish Breast Cancer Research GroupUniversity, hospital or other
- Collaborators
- Roche Farma, S.A
- Study start
- 23 Oct 2012 (actual)
- Primary completion
- 19 Dec 2017 (actual)
- Study completion
- 19 Dec 2017 (actual)
- First posted
- 27 Nov 2012 (estimated)
- Results
- Posted 4 Dec 2019
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, post-authorization observational with prospective follow-up (EPA-SP) study. Will be involved 137 metastatic breast cancer patients or metastatic colorectal cancer. The hypertension will be evaluated as a predictor of efficacy of bevacizumab associated with chemotherapy, in terms of progression-free survival (PFS) (Main endpoint).
The duration of the study will be approximately 42 months.
Detailed description
Hypertension (HT) is the most common side effect seen in trials of bevacizumab in combination with chemotherapy. Based on the hypothesis that the development of hypertension during treatment would be an indicative of the successful blockade of the Vascular Endothelial Growth Factor (VEGF) pathway, different studies have explored retrospectively the relationship between hypertension and the results of treatment with bevacizumab.
This study aims to demonstrate the association between hypertension (diagnosed optimally) with efficacy to treatment with bevacizumab prospectively and secondly verify if blood pressure measures taken at home are a reflection of a diagnosis of hypertension.
Also have been explored different molecular markers involved in the pathway of VEGF which might be used as predictors of response. Therefore, this study includes the collection of blood samples (serum or plasma) and tumor tissue of patients included in this study, with the aim of exploring biomarkers that correlate with treatment efficacy and toxicity.
The diagnosis of hypertension (HT) will be performed using a Holter recording, and standard blood pressure footage will be collected during the first three cycles of treatment given the Common Toxicity Criteria of the National Cancer Institute-NCI CTCAE version 4.0 and the guidelines of the European Society of Cardiology and Hypertension, 2007.
Will be collected a sample of primary tumor and blood for patients who previously have consented it. Samples will be sent to a central laboratory for analysis of biomarkers.
An interim analysis will be conducted to assess the true incidence of hypertension. Based on this analysis, will be evaluated the need to recalculate the sample size.
At the end of the study, will be performed an analysis of correlation of data measured by standard BP (Blood Pressure) and Holter recording footage with the PFS. Moreover will be determined in serum, plasma and tumor tissue and certain biomarkers to correlate with efficacy to treatment with bevacizumab.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab + Chemotherapy | – | –Patients who received the addition of Bevacizumab (BV) every 2-3 weeks to Chemotherapy (CT) with either oxaliplatin or irinotecan plus fluoropyrimidines in patients with Metastatic Colorectal Cancer (MCRC), either paclitaxel or capecitabine in patients with Metastatic Breast Cancer (MBC), as first-line therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with metastatic (disseminated at the time of diagnosis) breast cancer or colorectal cancer, treated with bevacizumab.
Key inclusion criteria (7 listed)
- May only participate in the study patients (women and men) who meet all the following criteria:
- MCC or MBC patients with chemotherapy and bevacizumab established indication. The first line systemic treatment planned for patients with MCC should be based in combination chemotherapy (oxaliplatin / irinotecan plus fluoropyrimidine) associated with bevacizumab. The first line systemic treatment planned for MBC patients should be based on a combination of paclitaxel or capecitabine plus bevacizumab.
- Presence of measurable or evaluable disease according to RECIST 1.1, for the evaluation of the response to treatment.
- Equal or more than 18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (8 listed)
- Have received prior systemic anticancer therapy with chemotherapy for advanced disease or prior treatment with bevacizumab.
- Treatment with an investigational agent or biological agent within 30 days prior to inclusion in the study.
- Contraindications to treatment with chemotherapy and bevacizumab according to summary products characteristics.
- Background or current history (within five years before the start of treatment) of other malignancies, except for colorectal carcinoma and breast cancer (patients with basal cell carcinoma or squamous cell skin or cervical carcinoma in situ treated curative may be included in the study).
- Life expectancy less than 3 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of Participants With or Without Blood Pressure Increase as a Predictor of Progression Free Survival (PFS)
Time frame: Up to 3 years
The incidence of hypertension was studied during treatment with bevacizumab combined with chemotherapy. A Cox regression analysis was performed, entering as a dependent variable the PFS and as independent variable the Arterial Hypertension (AHT) (yes/no). AHT is introduced in the model of Cox as a time-dependent variable since its situation can change as length of the study. The date on which the AHT changes (passes from normotensive to hypertensive).
Progression Free Survival (PFS)
Time frame: Up to 3 years
The PFS is the time from the patient receiving the first dose of chemotherapy for advanced disease to the date of progression, the administration of a new antineoplastic treatment that does not contain bevacizumab or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
2 secondary outcomes
Number of Participants With "White Coat" AHT While at Home
Time frame: Cycle 1, cycle 2, and cycle 3, up to 9 weeks
Number of Participants With "White Coat" AHT With 24 Hours Ambulatory BP Measure
Time frame: Baseline, cycle 1, cycle 2, and cycle 3, up to 9 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38578537Rodriguez-Lescure A, Gallego J, Garcia-Alfonso P, Massuti B, Marquez R, Calvo L, Sanchez-Rovira P, Anton A, Chacon JI, Ciruelos E, Ponce JJ, Santaballa A, Valladares-Ayerbes M, Duenas MR, Alonso V, Aparicio J, Encinas S, Robles L, Escudero MJ, Caballero R, Bezares S, Garcia-Ortiz MV, Morales-Ruiz T, de la Haba-Rodriguez J. Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study. Clin Transl Oncol. 2024 Aug;26(8):1896-1907. doi: 10.1007/s12094-024-03411-w. Epub 2024 Apr 5.
- Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research GroupLink provided by the sponsor.
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CRC
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.
Study Director study director
Hospital General Universitario de Elche
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Colorectal Cancer and Metastatic Breast Cancer, run by Spanish Breast Cancer Research Group at 10 sites in Spain.
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 7 inclusion and 8 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 4 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Spain. 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?
Yes. Results are posted in the registry (first posted 4 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With or Without Blood Pressure Increase as a Predictor of Progression Free Survival (PFS) (time frame: Up to 3 years). The study lists 2 primary outcomes in all. 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 NCT01733628, which also lists 1 linked publication.
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 4 Dec 2019.