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Metastatic Breast CancerPhase 2GIM11-BERGINCT02175446

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

A Phase 2 study testing Bevacizumab and eribulin in people with Metastatic Breast Cancer and Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, run by Consorzio Oncotech at 17 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Bevacizumab and eribulin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
17 sitesItaly
Study dates
Sep 2014to Dec 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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.

Who cannot join

  • 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.
Show all 12Show fewer
  • 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)

Trial locations and contacts

17 sites in 1 country.

Clinical Research Technology contact

0039089301545

17 sites in 1 country

Italy17 sites, 17 recruiting

  • Azienda Ospedaliera Istituti Ospitalieri di Cremona

    Cremona, 26100

    Daniele Generali, MD

    Recruiting

  • Ospedale 'F. Spaziani'

    Frosinone, 03100

    Teresa Gamucci, MD

    Recruiting

  • I.R.C.C.S. A.O.U. San Martino - I.S.T.

    Genova, 16132

    Lucia Del Mastro, MD

    Recruiting

  • Ospedale Unico Versilia

    Lido di Camaiore, 55041

    Domenico Amoroso, MD

    Recruiting

  • Ospedale San Luca Istituto Tumori Toscano

    Lucca

    Michelangelo Russillo, MD

    Recruiting

  • A.O.R.N. "A. Cardarelli"

    Naples, 80131

    Ferdinando Riccardi, MD

    Recruiting

  • Istituto Nazionale Tumori - IRCCS "Fondazione G.Pascale"

    Naples, 80131

    Michelino De Laurentiis, MD

    Recruiting

  • Università degli Studi di Napoli "Federico II"

    Naples, 80131

    Raffaella Ruocco, MD

    Grazia Arpino, MD

    Recruiting

  • AORN - Ospedali dei Colli Monaldi-Cotugno - C.T.O.

    Naples, 83131

    Vincenzo Montesarchio, MD

    Recruiting

  • I.R.C.C.S. Fondazione Salvatore Maugeri

    Pavia, 27100

    Alberto Zambelli, MD

    Recruiting

  • Azienda Ospedaliera Universitaria Pisana - Ospedale S. Chiara

    Pisa, 956126

    Andrea Michelotti, MD

    Recruiting

  • Presidio Ospedaliero Felice Lotti Pontedera

    Pontedera, 56025

    Giacomo Allegrini, MD

    Recruiting

  • Ospedale civile di Macerata

    Province of Macerata, 62100

    Barbara Pistilli, MD

    Recruiting

  • Istituto Regina Elena per lo studio e la cura dei tumori

    Roma, 00144

    Francesco Cognetti, MD

    Recruiting

  • Azienda Ospedaleira Universitaria San Giovanni di Dio e Ruggi d'aragona

    Salerno, 84131

    Stefano Pepe, MD

    Recruiting

  • Ospedale 'SS. Trinità'

    Sora, 03039

    Teresa Gamucci, MD

    Recruiting

  • Azienda Ospedaliera Universitaria Santa Maria della Misericordia di Udine

    Udine, 33100

    Fabio Puglisi, MD

    Recruiting

Other trials in Italy

About this study

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

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.

Read the 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.

Being tested
Bevacizumab and eribulin
Keywords
Breast cancer, HER2Negative, Second line treatment, HER2-, MBC, Metastatic, Metastatic breast cancer, bevacizumab, eribulin, Human Epidermal Growth Factor Receptor 2-Negative
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bevacizumab and eribulinDrug

    Also called Halaven, Avastin

    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

Study groups in NCT02175446
Study groupRoleWhat they receive
Experimental1ExperimentalBevacizumab 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
Receives: Drug: Bevacizumab and eribulin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response rate

    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.

    Measured: 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 outcomes (6)

  1. Progression free survival

    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.

    Measured: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months

  2. Overall Survival

    OS is defined as the time from first dosing in second line to death from any cause.

    Measured: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months

  3. Clinical Benefit Rate

    Clinical Benefit Rate is the proportion of patients with a complete or partial response or with stable disease at 24 weeks.

    Measured: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months

  4. Duration of response

    Duration of response measures the length of the response in those patients who responded to treatment.

    Measured: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months

  5. Safety

    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.

    Measured: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months

  6. Quality of life

    QoL and symptom control will be assessed using the FACT-B questionnaire.

    Measured: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jun 2014 (estimated)
  2. Study startSep 2014
  3. Primary completionDec 2016 (estimated)
  4. Study completionDec 2017 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
61 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02175446
Sponsor's protocol ID
GIM11-BERGI
Other IDs
2013-003194-10
Acronym
GIM11-BERGI
Status last verified
Jun 2016
First submitted
9 Jun 2014
Last updated
15 Jun 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

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.

  • Greenberg PA, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK, Buzdar AU. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol. 1996 Aug;14(8):2197-205. doi: 10.1200/JCO.1996.14.8.2197.

    PubMed 8708708

  • Chia SK, Speers CH, D'yachkova Y, Kang A, Malfair-Taylor S, Barnett J, Coldman A, Gelmon KA, O'reilly SE, Olivotto IA. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer. 2007 Sep 1;110(5):973-9. doi: 10.1002/cncr.22867.

    PubMed 17647245

  • Hamilton A, Hortobagyi G. Chemotherapy: what progress in the last 5 years? J Clin Oncol. 2005 Mar 10;23(8):1760-75. doi: 10.1200/JCO.2005.10.034. No abstract available.

    PubMed 15755984

  • Perez EA. Impact, mechanisms, and novel chemotherapy strategies for overcoming resistance to anthracyclines and taxanes in metastatic breast cancer. Breast Cancer Res Treat. 2009 Mar;114(2):195-201. doi: 10.1007/s10549-008-0005-6. Epub 2008 Apr 29.

    PubMed 18443902

  • Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997 Feb;18(1):4-25. doi: 10.1210/edrv.18.1.0287. No abstract available.

    PubMed 9034784

  • Inai T, Mancuso M, Hashizume H, Baffert F, Haskell A, Baluk P, Hu-Lowe DD, Shalinsky DR, Thurston G, Yancopoulos GD, McDonald DM. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol. 2004 Jul;165(1):35-52. doi: 10.1016/S0002-9440(10)63273-7.

    PubMed 15215160

  • Baffert F, Le T, Sennino B, Thurston G, Kuo CJ, Hu-Lowe D, McDonald DM. Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. Am J Physiol Heart Circ Physiol. 2006 Feb;290(2):H547-59. doi: 10.1152/ajpheart.00616.2005. Epub 2005 Sep 19.

    PubMed 16172161

  • Kamba T, Tam BY, Hashizume H, Haskell A, Sennino B, Mancuso MR, Norberg SM, O'Brien SM, Davis RB, Gowen LC, Anderson KD, Thurston G, Joho S, Springer ML, Kuo CJ, McDonald DM. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006 Feb;290(2):H560-76. doi: 10.1152/ajpheart.00133.2005. Epub 2005 Sep 19.

    PubMed 16172168

  • Mancuso MR, Davis R, Norberg SM, O'Brien S, Sennino B, Nakahara T, Yao VJ, Inai T, Brooks P, Freimark B, Shalinsky DR, Hu-Lowe DD, McDonald DM. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest. 2006 Oct;116(10):2610-21. doi: 10.1172/JCI24612.

    PubMed 17016557

  • Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005 Feb 1;23(4):792-9. doi: 10.1200/JCO.2005.05.098.

    PubMed 15681523

  • Gray R, Bhattacharya S, Bowden C, Miller K, Comis RL. Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2009 Oct 20;27(30):4966-72. doi: 10.1200/JCO.2008.21.6630. Epub 2009 Aug 31.

    PubMed 19720913

  • Miles DW, Chan A, Dirix LY, Cortes J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3239-47. doi: 10.1200/JCO.2008.21.6457. Epub 2010 May 24.

    PubMed 20498403

  • Robert NJ, Dieras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. doi: 10.1200/JCO.2010.28.0982. Epub 2011 Mar 7.

    PubMed 21383283

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab and eribulin in people with Metastatic Breast Cancer and Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, run by Consorzio Oncotech at 17 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 15 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Clinical Research Technology (0039089301545), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02175446, which also lists 26 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2016.

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