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

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ClinicalTrials.gov Identifier: NCT02175446
Recruitment Status : Unknown
Verified June 2016 by Consorzio Oncotech.
Recruitment status was:  Recruiting
First Posted : June 26, 2014
Last Update Posted : June 15, 2016
Sponsor:
Collaborator:
Clinical Research Technology S.r.l.
Information provided by (Responsible Party):
Consorzio Oncotech

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Human Epidermal Growth Factor 2 Negative Carcinoma of Breast Drug: Bevacizumab and eribulin Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : September 2014
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine


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:
  • Halaven
  • Avastin




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02175446


Contacts
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Contact: Clinical Research Technology 0039089301545

Locations
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Italy
Azienda Ospedaliera Istituti Ospitalieri di Cremona Recruiting
Cremona, Italy, 26100
Principal Investigator: Daniele Generali, MD         
Ospedale `F. Spaziani` Recruiting
Frosinone, Italy, 03100
Principal Investigator: Teresa Gamucci, MD         
I.R.C.C.S. A.O.U. San Martino - I.S.T. Recruiting
Genova, Italy, 16132
Principal Investigator: Lucia Del Mastro, MD         
Ospedale Unico Versilia Recruiting
Lido di Camaiore, Italy, 55041
Principal Investigator: Domenico Amoroso, MD         
Ospedale San Luca Istituto Tumori Toscano Recruiting
Lucca, Italy
Principal Investigator: Michelangelo Russillo, MD         
Ospedale civile di Macerata Recruiting
Macerata, Italy, 62100
Principal Investigator: Barbara Pistilli, MD         
A.O.R.N. "A. Cardarelli" Recruiting
Naples, Italy, 80131
Principal Investigator: Ferdinando Riccardi, MD         
Università degli Studi di Napoli "Federico II" Recruiting
Naples, Italy, 80131
Contact: Raffaella Ruocco, MD         
Principal Investigator: Grazia Arpino, MD         
Istituto Nazionale Tumori - IRCCS "Fondazione G.Pascale" Recruiting
Napoli, Italy, 80131
Principal Investigator: Michelino De Laurentiis, MD         
AORN - Ospedali dei Colli Monaldi-Cotugno - C.T.O. Recruiting
Napoli, Italy, 83131
Principal Investigator: Vincenzo Montesarchio, MD         
I.R.C.C.S. Fondazione Salvatore Maugeri Recruiting
Pavia, Italy, 27100
Principal Investigator: Alberto Zambelli, MD         
Azienda Ospedaliera Universitaria Pisana - Ospedale S. Chiara Recruiting
Pisa, Italy, 956126
Principal Investigator: Andrea Michelotti, MD         
Presidio Ospedaliero Felice Lotti Pontedera Recruiting
Pontedera, Italy, 56025
Principal Investigator: Giacomo Allegrini, MD         
Istituto Regina Elena per lo studio e la cura dei tumori Recruiting
Roma, Italy, 00144
Principal Investigator: Francesco Cognetti, MD         
Azienda Ospedaleira Universitaria San Giovanni di Dio e Ruggi d'aragona Recruiting
Salerno, Italy, 84131
Principal Investigator: Stefano Pepe, MD         
Ospedale `SS. Trinità` Recruiting
Sora, Italy, 03039
Principal Investigator: Teresa Gamucci, MD         
Azienda Ospedaliera Universitaria Santa Maria della Misericordia di Udine Recruiting
Udine, Italy, 33100
Principal Investigator: Fabio Puglisi, MD         
Sponsors and Collaborators
Consorzio Oncotech
Clinical Research Technology S.r.l.
Investigators
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Principal Investigator: Grazia Arpino, MD Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli "Federico II"

Publications of Results:

Other Publications:
Cohen A, et al. Clinical outcomes in Bevacizumab (BV)-treated patients (pts) with metastatic colorectal cancer (mCRC): Results from ARIES observational cohort study (OCS) and confirmation of BRITE data on BV beyond progression (BBP). ASCO 2010
Saab TB, et al. Bevacizumab (BV) plus chemotherapy (CT) in 2nd line metastatic colorectal cancer (mCRC): Initial results from ARIES a second observational cohort study. ASCO 2010.

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Responsible Party: Consorzio Oncotech
ClinicalTrials.gov Identifier: NCT02175446     History of Changes
Other Study ID Numbers: GIM11-BERGI
2013-003194-10 ( EudraCT Number )
First Posted: June 26, 2014    Key Record Dates
Last Update Posted: June 15, 2016
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Consorzio Oncotech:
Breast cancer
HER2Negative
Second line treatment
HER2-
MBC
Metastatic
Metastatic breast cancer
bevacizumab
eribulin
Human Epidermal Growth Factor Receptor 2-Negative

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors