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 (Argo)

February 4, 2020 updated by: Hoffmann-La Roche

Observational and Prospective Study to Develop Predictive and Prognostic Tools for Optimizing Therapy With Bevacizumab Frontline Cancer Therapy in Patients With Metastatic HER 2-Negative and Aggressive Disease Criteria

This multicenter, observational, prospective study will identify a powerful and easy predictive/prognostic marker to use with participants under bevacizumab.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

111

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08024
        • Hospital Quiron Barcelona; Servicio de Oncologia
      • Granada, Spain, 18014
        • Hospital Universitario Virgen de las Nieves; Servicio de Oncologia
      • Jaen, Spain, 23007
        • Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
      • Leon, Spain, 24071
        • Complejo Asistencial Universitario de Leon; Servicio de Oncologia
      • Lerida, Spain, 25198
        • Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
      • Lugo, Spain, 27003
        • Hospital Lucus Augusti; Servicio de Oncologia
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre; Servicio de Oncologia
      • Madrid, Spain, 28006
        • Hospital Universitario de la Princesa; Servicio de Oncologia
      • Madrid, Spain, 28033
        • Centro Oncologico MD Anderson Internacional; Servicio de Oncologia
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz; Servicio de Oncologia
      • Murcia, Spain, 30008
        • Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia
      • Murcia, Spain, 30120
        • Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia
      • Navarra, Spain, 31008
        • Hospital de Navarra; Servicio de Oncologia
      • Salamanca, Spain, 37007
        • Hospital Clinico Universitario de Salamanca; Servicio de Oncologia
      • Segovia, Spain, 40002
        • Hospital General de Segovia; Servicio de Oncologia
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen Macarena; Servicio de Oncologia
      • Valencia, Spain, 46015
        • Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia
      • Valencia, Spain, 46017
        • Hospital Universitario Dr. Peset; Servicio de Oncologia
      • Zamora, Spain, 49021
        • Complejo Hospitalario Zamora- H. Virgen de la Concha; Servicio Oncologia
    • Castellon
      • Castellon de La Plana, Castellon, Spain, 12002
        • Hospital Provincial de Castellon; Servicio de Oncologia
    • Cordoba
      • Córdoba, Cordoba, Spain, 14004
        • Hospital Universitario Reina Sofia; Servicio de Oncologia
    • Guipuzcoa
      • San Sebastián, Guipuzcoa, Spain, 20014
        • Hospital de Donostia.; Servicio de Oncología Radioterápica
    • Islas Baleares
      • Palma De Mallorca, Islas Baleares, Spain, 07014
        • Hospital Universitario Son Espases; Servicio de Oncologia
    • LA Coruña
      • La Coruna, LA Coruña, Spain, 15006
        • Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia
    • LAS Palmas
      • Las Palmas de Gran Canaria, LAS Palmas, Spain, 35016
        • Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Participants with human epidermal growth factor receptor 2 (HER2)-negative aggressive metastatic breast cancer treated with standard first line chemotherapy with paclitaxel-bevacizumab.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Participants With Metastatic Breast Cancer
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.
Drug: Bevacizumab
Bevacizumab will be administered as per local clinical practice and local labeling.
Drug: Paclitaxel
Paclitaxel will be administered as per local clinical practice and local labeling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Clinical Benefit
Time Frame: 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).
During follow-up (up to 18 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Overall Response as Assessed Using RECIST v1.1
Time Frame: 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).
From Baseline up to end of study (up to 18 months)
Progression Free Survival (PFS) as Assessed Using RECIST v1.1
Time Frame: 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).
From Baseline up to end of study (up to 18 months)
Overall Survival
Time Frame: 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).
From Baseline up to end of study (up to 18 months)
Percentage of Participants With Adverse Events of Toxicity Grading 3 and/or 4
Time Frame: 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.
From Baseline up to end of study (up to 18 months)
Optimal Cut-off for Clinical Benefit
Time Frame: 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.
Baseline (within 21 days prior to Day 1 Cycle 1), 7 days prior to Day 1 Cycle 3 (Cycle length = 28 days)
Percentage of Participants With Overall Response (OR) as Assessed Using RECIST v1. in Prognostic Groups
Time Frame: 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.
Baseline (within 21 days prior to Day 1 Cycle 1), 7 days prior to Day 1 Cycle 3 (Cycle length = 28 days)
PFS as Assessed Using RECIST v1. in Prognostic Groups
Time Frame: 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.
From Baseline up to end of study (up to 18 months)
Mean CTC Count Levels
Time Frame: 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.
Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days])
Mean Carcinoembryonic Antigen (CEA) Levels
Time Frame: Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days])
Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days])
Mean Biomarker Cancer Antigen 15.3 (CA 15.3) Level
Time Frame: 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.
Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days])

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 9, 2015

Primary Completion (Actual)

December 3, 2018

Study Completion (Actual)

December 3, 2018

Study Registration Dates

First Submitted

November 20, 2015

First Submitted That Met QC Criteria

November 23, 2015

First Posted (Estimate)

November 24, 2015

Study Record Updates

Last Update Posted (Actual)

February 17, 2020

Last Update Submitted That Met QC Criteria

February 4, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ML29756
  • ROC-BEV-2015-01 (Other Identifier: Hoffmann-La Roche)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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