PAINTER: Polymorphism And INcidence of Toxicity in ERibulin Treatment

Sponsor

Oncologia Medica dell'Ospedale Fatebenefratelli (Other)

Overall Status

Completed

CT.gov ID

NCT02864030

Collaborator

Mario Negri Institute for Pharmacological Research (Other)

200

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer Toxicity Neurotoxicity Drug Toxicity Adverse Drug Event	Drug: ERIBULIN MESYLATE	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

200 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Health Services Research

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 Start Date :

May 1, 2014

Actual Primary Completion Date :

Dec 31, 2018

Actual Study Completion Date :

Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: Single arm with Eribulin mesylate	Drug: ERIBULIN MESYLATE 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. Other Names: HALAVEN

Arm

Intervention/Treatment

Other: Single arm with Eribulin mesylate

Drug: ERIBULIN MESYLATE

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.

Other Names:

HALAVEN

Outcome Measures

Primary Outcome Measures

Incidence, time of onset, severity and duration of all Adverse Events (AEs) experienced during treatment with Eribulin (any grade) [Trough study completion, an average of 1 year]
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.
Association between a set of selected polymorphisms and the onset of any grade peripheral neuropathy [Trough study completion, an average of 1 year]
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.
Treatment tolerability [Trough study completion, an average of 1 year]
Treatment tolerability will also be described in terms of dose intensity and dose schedule maintenance.
DOT (Duration Of Treatment) [Trough study completion, an average of 1 year]
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).
OS (Overall Survival) [Trough study completion, an average of 1 year]
OS will be calculated from the date of start of therapy to the date of death.

Other Outcome Measures

The European Organization for research and treatment of cancer Quality of Life Questionnaire EORTC QLQ - C30 [Trough study completion, an average of 1 year]
This is a kind of assessment to evaluate the quality of life of cancer patients during Eribulin treatment using unique measurements that share a common Unit of Measure
Breast Cancer-Specific Quality of Life Questionnaire QlQ - BR23 [Trough study completion, an average of 1 year]
This is a kind of assessment to evaluate the quality of life during Eribulin treatment using unique measurements that share a common Unit of Measure

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Comprensorio sanitario di Bolzano	Bolzano	Italy	39100
2	Istituti Ospitalieri di Cremona	Cremona	Italy	26100
3	Azienda Ospedaliera S. Croce e Carle	Cuneo	Italy	12100
4	A.O.U. Careggi	Firenze	Italy	50134
5	A.O. Vito Fazzi	Lecce	Italy	73100
6	Ospedale Civile di Legnano	Legnano	Italy	20025
7	Oncologia Medica Ospedale Fatebenefratelli	Milano	Italy	20121
8	ASL Salerno Presidio Ospedaliero Andrea Tortora	Pagani	Italy	84016
9	Fondazione IRCCS Policlinico San Matteo di Pavia	Pavia	Italy	27100
10	Azienda Ospedaliera di Piacenza	Piacenza	Italy	29100
11	POliclinico Universitario Campus Bio-Medico	Roma	Italy	00128
12	Fondazione Policlinico Tor Vergata	Roma	Italy	00133
13	Istituto Nazionale Tumori "Regina Elena" Oncologia Medica A	Roma	Italy	00144
14	Istituto Nazionale Tumori "Regina Elena" Oncologia medica B	Roma	Italy	00144
15	Policlinico Universitario Agostino Gemelli	Roma	Italy	00168
16	Azienda Ospedaliera Valtellina e Valchiavenna - Presidio di Sondrio	Sondrio	Italy	23100
17	ASL di FRosinone Ospedale SS Trinità di Sora	Sora	Italy	03039
18	A.O. Santa Maria di Terni	Terni	Italy	5100
19	Ospedale di Treviglio	Treviglio	Italy	24047
20	Azienda Ospedaliero-Universitaria Santa Maria della Misericordia	Udine	Italy	33100

Sponsors and Collaborators

Oncologia Medica dell'Ospedale Fatebenefratelli
Mario Negri Institute for Pharmacological Research

Investigators

Study Chair: Laboratory of Clinical Research Department of Oncology IRCCS, Istituto Di Ricerche Farmacologiche Mario Negri
Study Chair: Giovanna Damia, PHD, Istituto Di Ricerche Farmacologiche Mario Negri