PAINTER: Polymorphism And INcidence of Toxicity in ERibulin Treatment

Study Overview
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Brief Summary
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On March 17th, 2011, the European Commission issued a marketing authorization valid throughout the European Union for Eribulin mesylate (Halaven; Eisai Limited), for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least two chemotherapic regimens for advanced disease. As the use of Eribulin will be widespread in this tumor setting, a better knowledge of its safety profile outside clinical trials is warranted. Indeed the possibility to select patients at risk for developing Eribulin-induced neuropathy, will allow the exclusion from these treatment of those patients harbouring the specific single nucleotide polymorphism (SNP). Given that Eribulin toxicity often results in treatment discontinuation, the ability to anticipate which patients will experience severe toxicity could allow for either early intervention or even possibly for prophylactic therapy, or for selection of the patients to be treated.

Detailed Description
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This study is primarily aimed at surveying the tolerability profile of Eribulin in an unselected population of patients with metastatic breast cancer in relation to toxicities already described in clinical trials, and neurotoxicity in particular. The secondary objectives of this trial include: To study the relationship between specific genetic polymorphism and incidence and severity of peripheral neuropathy To describe treatment efficacy in terms of duration of treatment and impact on survival. All toxicities will be collected and classified according to National Cancer Institute Common Terminology criteria for Adverse Events (NCI CTCAE) version 4.0 and monitored during all the treatment period and up to 30 days after therapy discontinuation. In particular, evaluation of incidence and outcome of any grade AEs already recorded in previous clinical trials will be collected, as follows: asthenia/fatigue, neutropenia, alopecia, nausea, peripheral neuropathy constipation Any other unexpected AEs shall be evaluated likewise. Patients must be followed for AEs until every ongoing Eribulin-related/unrelated toxicity and AE have been resolved, or the Investigator assesses them as chronic or stable or until the end of the trial, whichever comes first. For patients who will begin a new anticancer therapy after the last study drug administration, the AEs reporting period will end at the time the new treatment starts. For the determination of polymorphisms, a routine blood collection of two tubes with 3-5 ml of blood be performed. The sample can be collected at any time during the participant's first two treatment cycles. Blood will be collected in a Vacutainer containing ethylendiaminetetraacetic acid (EDTA). Immediately after blood collection, tubes have to be inverted (at least five times) and then stored at - 20° C.

Official Title
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Multicenter, Interventional, Single-arm, Phase IV Study Evaluating Tolerability of Eribulin and Its Relationship With a Set of Polymorphisms in an Unselected Population of Female Patients With Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer, Toxicity, Neurotoxicity, Drug Toxicity, Adverse Drug Event

Intervention / Treatment
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* Drug: ERIBULIN MESYLATE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of metastatic breast cancer Previous treatment with anthracyclines and taxanes Patients who will start Eribulin or who have already received only the first dose (cycle 1, day 1) of Eribulin according to the approved indication Ability to comply with sample collection Patient has signed the study Informed Consent Form (ICF) and the specific Pharmacogenetic ICF. Absence of any contraindication to treatment Exclusion Criteria: Previous treatment with Eribulin in a previous line of treatment Previous treatment with Eribulin off label

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single arm with Eribulin mesylate<br> | Drug: ERIBULIN MESYLATE<br>* Eribulin mesylate will be administered according to the European Medicines Agency (EMA) and Italian Medicines Agency (AIFA) approved indications and schedule consists in 1.23 mg/m2 on day 1 and on day 8 of each cycle. Cycles will be repeated every 21 days until progression of disease, unacceptable toxicity, patient refusal or medical decision. The decision to treat patients with Eribulin is independent from the trial. Patients will be treated and managed according to clinical practice. The physician can choose any further line of treatment after disease progression with Eribulin.<br>* Other names: HALAVEN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, time of onset, severity and duration of all Adverse Events (AEs) experienced during treatment with Eribulin (any grade) | All toxicities and their grade will be reported according to Common Terminology criteria for Adverse Events (CTCAE) v4.0, especially the most common AEs reported in previous clinical studies (asthenia/fatigue, neutropenia, alopecia, nausea, peripheral neuropathy and constipation) but also other possible unexpected toxicities. | Trough study completion, an average of 1 year | 
| Association between a set of selected polymorphisms and the onset of any grade peripheral neuropathy | The association between a set of selected polymorphisms and the onset of all grades peripheral neuropathy will be investigated using blood samples collected at the time of treatment initiation. | Trough study completion, an average of 1 year | 
| Treatment tolerability | Treatment tolerability will also be described in terms of dose intensity and dose schedule maintenance. | Trough study completion, an average of 1 year | 
| DOT (Duration Of Treatment) | DOT will be calculated for each patient from the date of start of Eribulin treatment to the date of last Eribulin administration for any cause (i.e. progression of disease, unacceptable toxicity, patient refusal or physician decision). | Trough study completion, an average of 1 year | 
| OS (Overall Survival) | OS will be calculated from the date of start of therapy to the date of death. | Trough study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eribulin mesylate, Halaven, Polymorphisms, Tolerability