An observational study in Metastatic Colorectal Cancer and Metastatic Breast Cancer, sponsored by Spanish Breast Cancer Research Group. Completed at 10 sites in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-12-04.
Sponsored by Spanish Breast Cancer Research Group · Observational
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.
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.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 143 is below the median of 184 across 2,642 observational studies indexed under Breast Neoplasms.
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Patients with metastatic (disseminated at the time of diagnosis) breast cancer or colorectal cancer, treated with bevacizumab.
May only participate in the study patients (women and men) who meet all the following criteria:
Exclusion Criteria:
Patients meeting any of the following circumstances will be excluded from the study:
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.
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).
Time frame: 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.
Time frame: Up to 3 years
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.
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
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.
Time frame: Baseline, cycle 1, cycle 2, and cycle 3, up to 9 weeks
From October 2012 to July 2016, 143 patients were included.
| Milestone | Bevacizumab + Chemotherapy |
|---|---|
| Started | 143 |
| Completed | 143 |
| Not completed | 0 |
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).
| Participants | Bevacizumab + Chemotherapy |
|---|---|
| No AHT : 0 to 0.5 years | 19 |
| No AHT : 0.5 to 1 years | 11 |
| No AHT : 1 to 1.5 years | 6 |
| No AHT : 1.5 to 2 years | 4 |
| No AHT : 2 to 2.5 years | 1 |
| No AHT: 2.5 to 3 years | 1 |
| Yes AHT: 0 to 0.5 years | 94 |
| Yes AHT: 0.5 to 1 years | 58 |
| Yes AHT: 1 to 1.5 years | 25 |
| Yes AHT: 1.5 to 2 years | 13 |
| Yes AHT: 2 to 2.5 years | 7 |
| Yes AHT: 2.5 to 3 years | 5 |
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.
| Months | Bevacizumab + Chemotherapy |
|---|---|
| Progression Free Survival (PFS) | 10.19 ± 8.77 |
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.
| Participants | Bevacizumab + Chemotherapy |
|---|---|
| White coat AHT in cycle 1 — No AHT | 60 |
| White coat AHT in cycle 1 — Yes AHT | 6 |
| White coat AHT in cycle 1 — Missing | 47 |
| White coat AHT in cycle 2 — No AHT | 73 |
| White coat AHT in cycle 2 — Yes AHT | 10 |
| White coat AHT in cycle 2 — Missing | 30 |
| White coat AHT in cycle 3 — No AHT | 65 |
| White coat AHT in cycle 3 — Yes AHT | 6 |
| White coat AHT in cycle 3 — Missing | 42 |
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.
| Participants | Bevacizumab + Chemotherapy |
|---|---|
| White coat AHT in baseline — No AHT | 94 |
| White coat AHT in baseline — Yes AHT | 14 |
| White coat AHT in baseline — Missing | 5 |
| White coat AHT in cycle 1 — No AHT | 66 |
| White coat AHT in cycle 1 — Yes AHT | 5 |
| White coat AHT in cycle 1 — Missing | 42 |
| White coat AHT in cycle 2 — No AHT | 83 |
| White coat AHT in cycle 2 — Yes AHT | 9 |
| White coat AHT in cycle 2 — Missing | 21 |
| White coat AHT in cycle 3 — No AHT | 70 |
| White coat AHT in cycle 3 — Yes AHT | 5 |
| White coat AHT in cycle 3 — Missing | 38 |
Collected over All adverse events occurred during the treatment and up to 30 days after the last dose were notified. All Serious Adverse Events (SAEs) that occurred within the first 3 cycles were recorded in the electronic Case Report Form (eCRF). Only those Grade 3-4 adverse events that were related to the treatment that occurred during the first 3 treatment cycles were recorded in the eCRF.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Bevacizumab + Chemotherapy | 9/143 (6.3%) | 22/135 (16.3%) | 57/135 (42.2%) |
| Event | Bevacizumab + Chemotherapy |
|---|---|
| DiarrheaGastrointestinal disorders | 5/135 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 2/135 |
| Soft tissue infectionInfections and infestations | 2/135 |
| Acute coronary syndromeCardiac disorders | 1/135 |
| Back painGeneral disorders | 1/135 |
| FeverGeneral disorders | 1/135 |
| GastroenteritisGastrointestinal disorders | 1/135 |
| ICTUSCardiac disorders | 1/135 |
| Skin infection: CellulitisInfections and infestations | 1/135 |
| Lynph Gland InfectionInfections and infestations | 1/135 |
| Event | Bevacizumab + Chemotherapy |
|---|---|
| Neutrophil count decreasedBlood and lymphatic system disorders | 12/135 |
| HypertensionCardiac disorders | 11/135 |
| GGT increasedInvestigations | 8/135 |
| Neutrophil Count DecreasedBlood and lymphatic system disorders | 3/135 |
| APTT increasedInvestigations | 3/135 |
| Abdominal painGastrointestinal disorders | 3/135 |
| FatigueGeneral disorders | 3/135 |
| LDL Cholesterol increasedMetabolism and nutrition disorders | 3/135 |
| LymphopeniaBlood and lymphatic system disorders | 2/135 |
| Mucositis oralGastrointestinal disorders | 2/135 |
| Age, Continuous(years) | Bevacizumab + Chemotherapy |
|---|---|
| Median | 61.18 (32.57 to 85.32) |
| Sex: Female, Male(Participants) | Bevacizumab + Chemotherapy |
|---|---|
| Female | 102 |
| Male | 41 |
| Race and Ethnicity Not Collected(Participants) | Bevacizumab + Chemotherapy |
|---|
| Region of Enrollment(participants) | Bevacizumab + Chemotherapy |
|---|---|
| Spain | 143 |
| Eastern Cooperative Oncology Group (ECOG) status(Participants) | Bevacizumab + Chemotherapy |
|---|---|
| ECOG 0 | 67 |
| ECOG 1 | 72 |
| Unknown | 4 |
| Blood Pressure Systolic(mmHg) | Bevacizumab + Chemotherapy |
|---|---|
| Mean | 129.4 (80 to 216) |
| Blood Pressure Diastolic(mmHg) | Bevacizumab + Chemotherapy |
|---|---|
| Mean | 74.73 (50 to 121) |
| Pulse(bpm) | Bevacizumab + Chemotherapy |
|---|---|
| Mean | 78.92 (52 to 128) |
3 further baseline measures are reported on the registry.
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Spanish Breast Cancer Research Group