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

Sponsor

Consorzio Oncotech (Other)

Overall Status

Unknown status

CT.gov ID

NCT02175446

Collaborator

Clinical Research Technology S.r.l. (Industry)

Enrollment

Locations

Arm

Duration (Months)

3.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

61 participants

Allocation:

N/A

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 :

Sep 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall Response rate [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

Progression free survival [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.
Overall Survival [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.
Clinical Benefit Rate [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.
Duration of response [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.
Safety [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.
Quality of life [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Azienda Ospedaliera Istituti Ospitalieri di Cremona	Cremona	Italy	26100
2	Ospedale 'F. Spaziani'	Frosinone	Italy	03100
3	I.R.C.C.S. A.O.U. San Martino - I.S.T.	Genova	Italy	16132
4	Ospedale Unico Versilia	Lido di Camaiore	Italy	55041
5	Ospedale San Luca Istituto Tumori Toscano	Lucca	Italy
6	Ospedale civile di Macerata	Macerata	Italy	62100
7	A.O.R.N. "A. Cardarelli"	Naples	Italy	80131
8	Università degli Studi di Napoli "Federico II"	Naples	Italy	80131
9	Istituto Nazionale Tumori - IRCCS "Fondazione G.Pascale"	Napoli	Italy	80131
10	AORN - Ospedali dei Colli Monaldi-Cotugno - C.T.O.	Napoli	Italy	83131
11	I.R.C.C.S. Fondazione Salvatore Maugeri	Pavia	Italy	27100
12	Azienda Ospedaliera Universitaria Pisana - Ospedale S. Chiara	Pisa	Italy	956126
13	Presidio Ospedaliero Felice Lotti Pontedera	Pontedera	Italy	56025
14	Istituto Regina Elena per lo studio e la cura dei tumori	Roma	Italy	00144
15	Azienda Ospedaleira Universitaria San Giovanni di Dio e Ruggi d'aragona	Salerno	Italy	84131
16	Ospedale 'SS. Trinità'	Sora	Italy	03039
17	Azienda Ospedaliera Universitaria Santa Maria della Misericordia di Udine	Udine	Italy	33100