Clinical trial NCT02864030: PAINTER: Polymorphism And INcidence of Toxicity in ERibulin Treatment
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Metastatic Breast Cancer
Toxicity
Neurotoxicity
Drug Toxicity
Adverse Drug Event
Keywords: Eribulin mesylate
Halaven
Polymorphisms
Tolerability
Lead sponsor: Oncologia Medica dell'Ospedale Fatebenefratelli
Sponsor class: OTHER_GOV
Collaborators: name: Mario Negri Institute for Pharmacological Research
First posted: 2016-08-11
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence, time of onset, severity and duration of all Adverse Events (AEs) experienced during treatment with Eribulin (any grade)
timeFrame: Trough study completion, an average of 1 year
measure: Association between a set of selected polymorphisms and the onset of any grade peripheral neuropathy
timeFrame: Trough study completion, an average of 1 year
measure: Treatment tolerability
timeFrame: Trough study completion, an average of 1 year
measure: DOT (Duration Of Treatment)
timeFrame: Trough study completion, an average of 1 year
measure: OS (Overall Survival)
timeFrame: Trough study completion, an average of 1 year
Secondary outcomes:
Other outcomes:
measure: The European Organization for research and treatment of cancer Quality of Life Questionnaire EORTC QLQ - C30
timeFrame: Trough study completion, an average of 1 year
measure: Breast Cancer-Specific Quality of Life Questionnaire QlQ - BR23
timeFrame: Trough study completion, an average of 1 year
Locations:
city: Bolzano
country: Italy
facility: Comprensorio sanitario di Bolzano
city: Cremona
country: Italy
facility: Istituti Ospitalieri di Cremona
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S. Croce e Carle
city: Firenze
country: Italy
facility: A.O.U. Careggi
city: Lecce
country: Italy
facility: A.O. Vito Fazzi
city: Legnano
country: Italy
facility: Ospedale Civile di Legnano
city: Milano
country: Italy
facility: Oncologia Medica Ospedale Fatebenefratelli
city: Pagani
country: Italy
facility: ASL Salerno Presidio Ospedaliero Andrea Tortora
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo di Pavia
city: Piacenza
country: Italy
facility: Azienda Ospedaliera di Piacenza
city: Roma
country: Italy
facility: POliclinico Universitario Campus Bio-Medico
city: Roma
country: Italy
facility: Fondazione Policlinico Tor Vergata
city: Roma
country: Italy
facility: Istituto Nazionale Tumori "Regina Elena" Oncologia Medica A
city: Roma
country: Italy
facility: Istituto Nazionale Tumori "Regina Elena" Oncologia medica B
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Sondrio
country: Italy
facility: Azienda Ospedaliera Valtellina e Valchiavenna - Presidio di Sondrio
city: Sora
country: Italy
facility: ASL di FRosinone Ospedale SS Trinità di Sora
city: Terni
country: Italy
facility: A.O. Santa Maria di Terni
city: Treviglio
country: Italy
facility: Ospedale di Treviglio
city: Udine
country: Italy
facility: Azienda Ospedaliero-Universitaria Santa Maria della Misericordia
Study officials:
affiliation: Istituto Di Ricerche Farmacologiche Mario Negri
name: Laboratory of Clinical Research Department of Oncology IRCCS
role: STUDY_CHAIR
affiliation: Istituto Di Ricerche Farmacologiche Mario Negri
name: Giovanna Damia, PHD
role: STUDY_CHAIR
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