Clinical trial NCT02175446: Safety and Efficacy Study of Eribulin in Combination With Bevacizumab for Second-line Treatment HER2- MBC Patients
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
Keywords: Breast cancer
HER2Negative
Second line treatment
HER2-
MBC
Metastatic
Metastatic breast cancer
bevacizumab
eribulin
Human Epidermal Growth Factor Receptor 2-Negative
Lead sponsor: Consorzio Oncotech
Sponsor class: OTHER
Collaborators: name: Clinical Research Technology S.r.l.
First posted: 2014-06-26
Enrollment: 61
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Overall Response rate
timeFrame: 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:
measure: Progression free survival
timeFrame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
measure: Overall Survival
timeFrame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
measure: Clinical Benefit Rate
timeFrame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
measure: Duration of response
timeFrame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
measure: Safety
timeFrame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
measure: Quality of life
timeFrame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 30 months
Other outcomes:
Locations:
city: Cremona
country: Italy
facility: Azienda Ospedaliera Istituti Ospitalieri di Cremona
city: Frosinone
country: Italy
facility: Ospedale 'F. Spaziani'
city: Genova
country: Italy
facility: I.R.C.C.S. A.O.U. San Martino - I.S.T.
city: Lido di Camaiore
country: Italy
facility: Ospedale Unico Versilia
city: Lucca
country: Italy
facility: Ospedale San Luca Istituto Tumori Toscano
city: Macerata
country: Italy
facility: Ospedale civile di Macerata
city: Naples
country: Italy
facility: A.O.R.N. "A. Cardarelli"
city: Naples
country: Italy
facility: Università degli Studi di Napoli "Federico II"
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori - IRCCS "Fondazione G.Pascale"
city: Napoli
country: Italy
facility: AORN - Ospedali dei Colli Monaldi-Cotugno - C.T.O.
city: Pavia
country: Italy
facility: I.R.C.C.S. Fondazione Salvatore Maugeri
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana - Ospedale S. Chiara
city: Pontedera
country: Italy
facility: Presidio Ospedaliero Felice Lotti Pontedera
city: Roma
country: Italy
facility: Istituto Regina Elena per lo studio e la cura dei tumori
city: Salerno
country: Italy
facility: Azienda Ospedaleira Universitaria San Giovanni di Dio e Ruggi d'aragona
city: Sora
country: Italy
facility: Ospedale 'SS. Trinità'
city: Udine
country: Italy
facility: Azienda Ospedaliera Universitaria Santa Maria della Misericordia di Udine
Study officials:
affiliation: Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli "Federico II"
name: Grazia Arpino, MD
role: PRINCIPAL_INVESTIGATOR
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