A Study to Develop Predictive and Prognostic Tools for Optimizing Therapy With Bevacizumab Frontline Cancer Therapy in Participants With HER 2-Negative Aggressive Metastatic Breast Cancer
- Registration Number
- NCT02613208
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This multicenter, observational, prospective study will identify a powerful and easy predictive/prognostic marker to use with participants under bevacizumab.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 111
- Participants with HER2-negative metastatic breast cancer. Mandatory to have the HER2/estrogen receptor (ER)/progesterone receptor (PR) status
- Participant who met criteria for first-line treatment with chemotherapy plus bevacizumab (standard doses) by local, regional or national guidelines or authorities
- Participants with measurable disease (RECIST criteria v1.1) or participants with no measurable but assessable disease
- Molecular phenotype as triple negative metastatic breast cancer; and ER-positive tumors need to fulfill at least one of the two clinical criteria: metastatic relapse on adjuvant endocrine therapy or progression to at least one prior line of endocrine therapy for advanced disease; or aggressive disease criteria (at least two criteria): taxane based regimen in the (neo) adjuvant setting; metastatic relapse within 2 years from the end of chemotherapy for early breast cancer; liver metastasis; three or more organs with metastatic involvement; symptomatic visceral disease
- Eastern Cooperative Oncology Group (ECOG) 0-2
- Participant has received prior chemotherapy for metastatic disease
- Participant requiring major/minor surgery within 3 weeks prior to administration of the first dose of study treatment
- Participant has received an investigational therapy within 4 weeks prior to study entry
- Participant has known symptomatic brain metastases
- Participant with non-measurable or assessable disease: exclusive blastic bone disease; pleural, pericardial or abdominal effusion as only evidence of disease
- Participant in chronic daily treatment with corticosteroids (doses greater than [>]10 milligrams per day [mg/day] of methylprednisolone or equivalent), except inhaled steroids
- Pregnant or breastfeeding participant
- Women of childbearing potential who are not using hormonal contraceptives or highly effective birth control during the study
- Participant has an active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- Participant with significant renal, hematological or liver function alteration according to investigator's criteria
- Participant has serious medical risk factors involving any of the major organ systems
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Participants With Metastatic Breast Cancer Bevacizumab Participants with metastatic breast cancer receiving bevacizumab in combination with paclitaxel, will be observed for treatment responses for up to 18 months from the start of treatment. Participants With Metastatic Breast Cancer Paclitaxel Participants with metastatic breast cancer receiving bevacizumab in combination with paclitaxel, will be observed for treatment responses for up to 18 months from the start of treatment.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Clinical Benefit During follow-up (up to 18 months) Clinical benefit was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). Clinical benefit is defined as partial or complete response as well as tumor stabilization for up to 24 weeks. Results for clinical benefit were reported for 2 groups based on Circulating Tumor Cells (CTC) Levels. The Sensitive group had CTC levels \<5 (\<5 CTCs in one of the two determinations) and Resistant group had CTC ≥5 (≥ 5 CTCs in the two determinations).
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Overall Response as Assessed Using RECIST v1.1 From Baseline up to end of study (up to 18 months) Overall response = Complete Response (CR) + Partial Response (PR). Overall response was evaluated for the Sensitive group (CTC \<5) and Resistant group (CTC ≥5).
Progression Free Survival (PFS) as Assessed Using RECIST v1.1 From Baseline up to end of study (up to 18 months) PFS was evaluated for the Sensitive group (CTC \<5) and Resistant group (CTC ≥5).
Mean CTC Count Levels Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days]) CTC and CEA levels were compared to determine any correlation between the two. Both CTC count at baseline and at cycle 2 were considered.
Overall Survival From Baseline up to end of study (up to 18 months) OS was evaluated for the Sensitive group (CTC \<5) and Resistant group (CTC ≥5).
Percentage of Participants With Adverse Events of Toxicity Grading 3 and/or 4 From Baseline up to end of study (up to 18 months) Adverse events (AEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v 4.0). Any AEs that are not specifically listed in the NCI CTCAE follow the logic - Grade 3) Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4: Life-threatening consequences or urgent intervention indicated.
Optimal Cut-off for Clinical Benefit Baseline (within 21 days prior to Day 1 Cycle 1), 7 days prior to Day 1 Cycle 3 (Cycle length = 28 days) Clinical benefit was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). Clinical benefit is defined as partial or complete response as well as tumor stabilization for up to 24 weeks. The optimal cut-off for clinical benefit was calculated from a Receiver Operating Curve (ROC) based on CTC level and used to define the prognostic factors that could better predict clinical outcomes.
Percentage of Participants With Overall Response (OR) as Assessed Using RECIST v1. in Prognostic Groups Baseline (within 21 days prior to Day 1 Cycle 1), 7 days prior to Day 1 Cycle 3 (Cycle length = 28 days) Overall response = CR + PR. An optimal cut-off point for the CTC count of 0.5 after 2 cycles of treatment was used to define the prognostic groups.
PFS as Assessed Using RECIST v1. in Prognostic Groups From Baseline up to end of study (up to 18 months) An optimal cut-off point for the CTC count of 0.5 after 2 cycles of treatment was used to define the prognostic groups.
Mean Carcinoembryonic Antigen (CEA) Levels Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days]) Mean Biomarker Cancer Antigen 15.3 (CA 15.3) Level Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days]) CTC and CA 15.3 levels were compared to determine any correlation between the two. Both CTC count at baseline and at cycle 2 were considered.
Trial Locations
- Locations (25)
Hospital Provincial de Castellon; Servicio de Oncologia
🇪🇸Castellon de La Plana, Castellon, Spain
Hospital Universitario Son Espases; Servicio de Oncologia
🇪🇸Palma De Mallorca, Islas Baleares, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia
🇪🇸La Coruna, LA Coruña, Spain
Hospital Universitario Reina Sofia; Servicio de Oncologia
🇪🇸Córdoba, Cordoba, Spain
Hospital de Donostia.; Servicio de Oncología Radioterápica
🇪🇸San Sebastián, Guipuzcoa, Spain
Hospital Quiron Barcelona; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Universitario Virgen de las Nieves; Servicio de Oncologia
🇪🇸Granada, Spain
Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
🇪🇸Jaen, Spain
Complejo Asistencial Universitario de Leon; Servicio de Oncologia
🇪🇸Leon, Spain
Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
🇪🇸Lerida, Spain
Hospital Lucus Augusti; Servicio de Oncologia
🇪🇸Lugo, Spain
Centro Oncologico MD Anderson Internacional; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario de la Princesa; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario La Paz; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital de Navarra; Servicio de Oncologia
🇪🇸Navarra, Spain
Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia
🇪🇸Murcia, Spain
Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia
🇪🇸Murcia, Spain
Hospital Clinico Universitario de Salamanca; Servicio de Oncologia
🇪🇸Salamanca, Spain
Hospital General de Segovia; Servicio de Oncologia
🇪🇸Segovia, Spain
Hospital Universitario Virgen Macarena; Servicio de Oncologia
🇪🇸Sevilla, Spain
Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia
🇪🇸Valencia, Spain
Hospital Universitario Dr. Peset; Servicio de Oncologia
🇪🇸Valencia, Spain
Complejo Hospitalario Zamora- H. Virgen de la Concha; Servicio Oncologia
🇪🇸Zamora, Spain
Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia
🇪🇸Las Palmas de Gran Canaria, LAS Palmas, Spain