Safety and Efficacy Study of Eribulin in Combination With Bevacizumab for Second-line Treatment HER2- MBC Patients (GIM11-BERGI)

June 14, 2016 updated by: Consorzio Oncotech

A Phase II Single Arm Trial Evaluating the Efficacy and Safety of Eribulin in Combination With Bevacizumab for 2-Line Treatment of HER 2-Negative Metastatic Breast Cancer Progressing After 1-Line Therapy With Bevacizumab and Paclitaxel

In the second-line treatment setting for MBC, many agents, including antitubulin drugs (Taxanes, Vinorelbine) and antimetabolites (Capecitabine, Gemcitabine), have demonstrated activity, but no agent is clearly superior. Although some combinations of cytotoxic agents provide a small progression-free survival advantage, none has demonstrated an OS advantage, and toxicity is generally greater than for single agents. At present, there is no standard for this treatment setting. New treatments that could delay disease progression without systemic toxicity would represent a significant advancement.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Metastatic breast cancer (MBC) is incurable, and the majority of patients succumb to their disease within 2 years of diagnosis.

Patients with MBC usually receive treatment with endocrine or cytotoxic chemotherapeutic agents, and treatment decisions are generally guided by the hormone receptor and Human Epidermal Growth Factor Receptor 2-Negative status of the disease, the number and location of metastases, and prior treatment history in both adjuvant and metastatic settings. In first- and second-line treatment settings of Metastatic Breast Cancer, numerous cytotoxic chemotherapy agents have demonstrated activity, including anti-tubulin drugs (Taxanes, Vinorelbine), Anthracyclines, and anti-metabolites (Capecitabine, Gemcitabine). However, no single agent has demonstrated a clear survival advantage over another, and use of sequential single-agent therapies is the most frequent approach. The choice of chemotherapy agent(s) is often determined by a number of factors, including history of prior therapy, treatment-free interval, and patient preference. Thus, no single standard treatment exists for patients with advanced disease. Patients who progress during or after their first treatment for Metastatic Brest Cancer typically have a short progression-free interval of 4-6 months and survive for 8-12 months. New treatment modalities are needed to improve clinical outcome and maintain the quality of life for these patients.

Study Type

Interventional

Enrollment (Anticipated)

61

Phase

  • Phase 2

Contacts and Locations

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

Study Contact

  • Name: Clinical Research Technology
  • Phone Number: 0039089301545

Study Locations

  • Italy
      • Cremona, Italy, 26100
        • Recruiting
        • Azienda Ospedaliera Istituti Ospitalieri di Cremona
        • Principal Investigator:
          • Daniele Generali, MD
      • Frosinone, Italy, 03100
        • Recruiting
        • Ospedale 'F. Spaziani'
      • Genova, Italy, 16132
        • Recruiting
        • I.R.C.C.S. A.O.U. San Martino - I.S.T.
      • Lido di Camaiore, Italy, 55041
        • Recruiting
        • Ospedale Unico Versilia
      • Lucca, Italy
        • Recruiting
        • Ospedale San Luca Istituto Tumori Toscano
        • Principal Investigator:
          • Michelangelo Russillo, MD
      • Macerata, Italy, 62100
        • Recruiting
        • Ospedale Civile di Macerata
        • Principal Investigator:
          • Barbara Pistilli, MD
      • Naples, Italy, 80131
        • Recruiting
        • A.O.R.N. "A. Cardarelli"
      • Naples, Italy, 80131
        • Recruiting
        • Università degli Studi di Napoli "Federico II"
        • Contact:
          • Raffaella Ruocco, MD
      • Napoli, Italy, 80131
        • Recruiting
        • Istituto Nazionale Tumori - IRCCS "Fondazione G.Pascale"
      • Napoli, Italy, 83131
        • Recruiting
        • AORN - Ospedali dei Colli Monaldi-Cotugno - C.T.O.
      • Pavia, Italy, 27100
        • Recruiting
        • I.R.C.C.S. Fondazione Salvatore Maugeri
        • Principal Investigator:
          • Alberto Zambelli, MD
      • Pisa, Italy, 956126
        • Recruiting
        • Azienda Ospedaliera Universitaria Pisana - Ospedale S. Chiara
      • Pontedera, Italy, 56025
        • Recruiting
        • Presidio Ospedaliero Felice Lotti Pontedera
        • Principal Investigator:
          • Giacomo Allegrini, MD
      • Roma, Italy, 00144
        • Recruiting
        • Istituto Regina Elena per lo studio e la cura dei tumori
        • Principal Investigator:
          • FRANCESCO COGNETTI, mD
      • Salerno, Italy, 84131
        • Recruiting
        • Azienda Ospedaleira Universitaria San Giovanni di Dio e Ruggi d'aragona
        • Principal Investigator:
          • Stefano Pepe, MD
      • Sora, Italy, 03039
        • Recruiting
        • Ospedale 'SS. Trinità'
      • Udine, Italy, 33100
        • Recruiting
        • Azienda Ospedaliera Universitaria Santa Maria della Misericordia di Udine

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

Female

Description

Inclusion Criteria:

  • Signed informed consent prior to initiation of any study-specific procedures or treatment, as confirmation of the patient's awareness and willingness to comply with the study requirements.
  • Female patients ≥18 years of age.
  • Histologically confirmed Human Epidermal Growth Factor Receptor 2-Negative adenocarcinoma of the breast with documented progression of disease per investigator assessment following or during first-line treatment with Bevacizumab in combination with Paclitaxel for MBC; patients can have measurable or non-measurable disease. A minimum of 4 cycles of Bevacizumab 15 mg/kg or 6 cycles 10 mg/kg received in the first-line setting.
  • Patients must have received Bevacizumab in combination with Paclitaxel as first line treatment. As part of their first line maintenance treatment, patients may have received:
  • Bevacizumab monotherapy
  • Bevacizumab in combination with endocrine treatment
  • Nothing (for a period ≤ 6 weeks from the last Bevacizumab treatment)
  • ECOG performance status (PS) of 0-2.
  • At least 28 days since prior radiation therapy or surgery and recovery from treatment.
  • Patients must have measurable disease which must be evaluable per RECIST v1.1.
  • Estimated life expectancy of ≥12 weeks.

Exclusion Criteria:

Disease-specific exclusions

  • Patients who have received anti-angiogenic therapy [e.g. tyrosine kinase inhibitors (TKIs) or anti-vascular endothelial growth factors (anti-VEGFs)] other than Bevacizumab for the first-line treatment of MBC.
  • Patients who have exclusively received endocrine treatment in combination with Bevacizumab until the first progression.
  • Positive or unknown Human Epidermal Growth Factor Receptor 2/neu status or for whom determination of Human Epidermal Growth Factor Receptor 2 status is not possible. In general, Human Epidermal Growth Factor Receptor 2 positive status will be identified by a FISH assay as evaluated at the institution, or, if FISH is unavailable, a 2+ or 3+ immunohistochemistry result (but method of identification may vary by region or institution).
  • Current, recent (within 4 weeks or 2 half-lives, whichever is greater, before day 1) or planned participation in an experimental drug study - other than a Bevacizumab breast cancer study.
  • Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix or breast within the last 5 years.
  • Any laboratory values at baseline as described in the protocol;
  • Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would prevent the patient from meeting the study requirements.
  • Serious active infection requiring i.v. antibiotics and/or hospitalization at study entry.
  • Patients who are treated with any medicinal product that contraindicates the use of any of the study drugs, may interfere with the planned treatment, affects patient compliance or puts the patient at high risk for treatment-related complications.

Bevacizumab-specific exclusions: (see protocol)

Eribulin-specific exclusions: (see protocol)

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

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental1

Bevacizumab and eribulin

In this study all patients will receive:

  • Eribulin 1.23 mg/m2 on days 1, 8 every 3 weeks intravenously
  • Bevacizumab 15 mg/kg every 3 weeks intravenously or Bevacizumab 10 mg/kg every 2 weeks intravenously
Drug: Bevacizumab and eribulin
In this study, Bevacizumab and Eribulin are considered to be the "investigational study drugs". Bevacizumab is provided as 25 mg/ml concentrate for infusion. Vials contain 100 mg of Bevacizumab in 4 ml and/or 400 mg in 16 ml. Eribulin is provided as vials containing 1 mg/2 mL Eribulin as a 500 µg/mL solution in ethanol/water
Other Names:
  • Avastin
  • Halaven

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response rate
Time Frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
ORR will be evaluated for those patients who have a response to second-line treatment as defined per RECIST version 1.1 in patients with measurable disease according to RECIST version 1.1. ORR will be based on the best overall response (BOR) as defined by RECIST Guidelines v. 1.1.
Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
Second-line progression-free survival, defined as the time from first dosing to the first documented disease progression or death from any cause, whichever occurs first.
Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
Overall Survival
Time Frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
OS is defined as the time from first dosing in second line to death from any cause.
Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
Clinical Benefit Rate
Time Frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
Clinical Benefit Rate is the proportion of patients with a complete or partial response or with stable disease at 24 weeks.
Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
Duration of response
Time Frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
Duration of response measures the length of the response in those patients who responded to treatment.
Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
Safety
Time Frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
Safety of second line treatment will be evaluated by the frequency of AEs and SAEs, cardiac events, clinically significant abnormal laboratory tests, vital signs, and ECOG PS. All patients who received at least one dose of study treatment will be included in the safety analysis.
Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
Quality of life
Time Frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
QoL and symptom control will be assessed using the FACT-B questionnaire.
Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months

Collaborators and Investigators

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

Sponsor

Consorzio Oncotech

Collaborators

Clinical Research Technology S.r.l.

Investigators

  • Principal Investigator: Grazia Arpino, MD, Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli "Federico II"

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

September 1, 2014

Primary Completion (Anticipated)

December 1, 2016

Study Completion (Anticipated)

December 1, 2017

Study Registration Dates

First Submitted

June 9, 2014

First Submitted That Met QC Criteria

June 25, 2014

First Posted (Estimate)

June 26, 2014

Study Record Updates

Last Update Posted (Estimate)

June 15, 2016

Last Update Submitted That Met QC Criteria

June 14, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GIM11-BERGI
  • 2013-003194-10 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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