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Eribulin as 1st Line Treatment in Elderly Patients With Advanced Breast Cancer

Primary Purpose

Breast Cancer, Adenocarcinoma

Status

Terminated

Phase

Phase 2

Locations

Switzerland

Study Type

Interventional

Intervention

Eribulin mesilate

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Eribulin, Breast Cancer, Elderly Patient, Phase II Trial, HER2-neg, adenocarcinoma

Eligibility Criteria

70 Years - undefined (Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Patient must give written informed consent according to ICH/GCP regulations before registration
Histologically or cytologically confirmed locally advanced or metastatic HER2-neg, hormone receptor positive or negative adenocarcinoma of the breast with measurable or evaluable disease according to RECIST 1.1 criteria
At least 6 months since last adjuvant/neoadjuvant chemotherapy administration before registration
At least 2 weeks since prior radiotherapy or endocrine therapy and complete recovery from these interventions at time of registration
Baseline C-SGA and patient-reported outcome (PRO) forms have been completed
Female patient at the age of ≥70 years
WHO performance status 0-2
Adequate hematological values: hemoglobin ≥80 g/L (transfusions are allowed), neutrophils ≥1.5 x 109/L, platelets ≥ 100 x 109/L
Adequate hepatic function: bilirubin ≤1.5 x ULN, AST ≤3 x ULN, alkaline phosphatase (AP) ≤2.5 x ULN (in case of liver metastases ≤5 x ULN or in case of bone metastases ≤10 x ULN)
Adequate renal function (calculated creatinine clearance >40 mL/min, according to the formula of Cockcroft-Gault)

Exclusion Criteria:

Known CNS metastases
Previous malignancy within 3 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
Prior chemotherapy for advanced disease
Concurrent anticancer treatment or treatment in a clinical trial within 30 days prior to registration. Exception: participation in SAKK 96/12
Palliative irradiation prior to study entry with more than 30% of marrow-bearing bone irradiated
Pre-existing neuropathy ≥G2 (according to CTCAE v4.0) at registration
Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV (see Appendix 4), unstable angina pectoris, history of myocardial infarction within the last three months, significant arrhythmias, congenital long QT-syndrome)
Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information
Known hypersensitivity to trial drug or to any component of the trial drug
Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes)
Psychiatric disorder precluding understanding of trial information, giving informed consent, taking part in the geriatric assessment, or interfering with compliance/with the trial protocol
Any familial, sociological or geographical condition potentially hampering proper staging and compliance with the trial protocol

Sites / Locations

Kantonsspital Aarau
Kantonsspital Baden
Universitaetsspital-Basel
Praxis für ambulante Tumortherapie
Istituto Oncologico della Svizzera Italiana
Klinik Engeried / Oncocare
Inselspital, Bern
Spitalzentrum Biel
Kantonsspital Graubünden
Kantonsspital Frauenfeld / Brustzentrum Thurgau
HFR Fribourg - Hôpital cantonal
Clinique de Genolier
Centre Hospitalier Universitaire Vaudois
Clinica Sant'Anna - Oncologia Varini & Calderoni & Christinat
Kantonsspital Luzern
Onkologie Zentrum Spital Männedorf
Kantonsspital Olten
Rundum Onkologie am Bahnhofpark
Onkologiezentrum Bürgerspital Solothurn
Onkologiepraxis Dr. med. Isabella Schönenberger
Tumorzentrum ZeTUP
Kantonsspital - St. Gallen
Regionalspital
Kantonsspital Winterthur
Onkozentrum - Klinik im Park
Brust-Zentrum AG Zürich

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm: Eribulin mesilate

Arm Description

Outcomes

Primary Outcome Measures

Disease Control (DC)

A patient has DC, if she has complete response (CR) or partial response (PR) at any time point during treatment, or if she has stable disease (SD) for at least 24 weeks (according to RECIST v1.1).

Secondary Outcome Measures

Time to treatment failure (TTF)

time from registration until treatment discontinuation due to any reason or the occurrence of a second tumor. Patients still on treatment will be censored at the date of their last eribulin administration

Objective response (OR)

A patient is defined as having OR, if she has CR or PR according to RECIST v1.1 at any time point during treatment. For the primary analysis, all responses (CR, PR) will be considered, including unconfirmed responses. In a sensitivity analysis, only those responses for which a confirmatory measurement at least 4 weeks later is available will be counted as CR or PR

Time to progression (TTP)

TTP is defined as time from registration until documented progression according to RECIST v1.1 or death due to tumor. Patients not experiencing an event and patients starting a new anticancer therapy in the absence of an event will be censored at the date of their last available tumor assessment showing non-progression.

Overall survival (OS)

OS is defined as time from registration until death from any cause. Patients not experiencing an event will be censored at the last date they were known to be alive.

Adverse events (AEs)

AEs will be assessed according to NCI CTCAE v4.0.

Patient reported neuropathy (PRO Form) and characterization of patients based on cancer-specific geriatric assessment (C-SGA)

Full Information

NCT ID

NCT02404506

First Posted

March 26, 2015

Last Updated

September 27, 2021

Sponsor

Swiss Group for Clinical Cancer Research

1. Study Identification

Unique Protocol Identification Number

NCT02404506

Brief Title

Eribulin as 1st Line Treatment in Elderly Patients With Advanced Breast Cancer

Official Title

Eribulin as 1st Line Treatment in Elderly Patients (≥ 70 Years) With Advanced Breast Cancer: a Multicenter Phase II Trial

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Terminated

Why Stopped

The trial was prematurely terminated as of 22.07.2021 as per SAKK board decision board decision from 14th of November 2020. The trial was terminated after the primary endpoint was analyzed, which was the case end of December 2020.

Study Start Date

August 17, 2015 (Actual)

Primary Completion Date

December 30, 2020 (Actual)

Study Completion Date

July 22, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Swiss Group for Clinical Cancer Research

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Breast cancer is the most frequent malignancy in women, world-wide the leading cause of cancer mortality. One of the strongest risk factors for developing breast cancer is age, with a prevalence approaching 7% in women >70 years; more than 40% of breast cancer patients are older than 65 years. Although the survival rate has increased in the last years, about one third of patients will relapse with distant metastases. Treatment for patients with metastatic breast cancer is palliative, therefore maintaining or improving quality of life. The use of taxanes and anthracyclines as first line chemotherapy regimen for metastatic breast cancer is widely accepted. Both taxanes and anthracyclines have considerable side effects, especially in elderly patients. Eribulin, a synthetic analogue of a chemotherapeutically active compound derived from the sea sponge Halichondria okadai, acts as an inhibitor of microtubule dynamics. It is registered as palliative chemotherapy in advanced breast cancer after anthracyclines and taxanes. Studies with eribulin treatment have shown similar efficacy compared to anthracyclines and taxanes, but less toxicity. Those studies showed that often the dose of eribulin had to be reduced during treatment due to toxicity without compromising the efficacy of the treatment. The main objective of the trial is to explore the efficacy of a reduced starting dose of eribulin as first-line treatment in elderly metastatic breast cancer patients. The secondary objective of the trial is to investigate the safety of eribulin in those patients. Eribulin mesilate 1.1mg/m2 i.v. will be administered intravenously every 3 weeks on day 1 and day 8 until progressive disease.

Detailed Description

Due to a rising number of elderly patients, fit for chemotherapy, investigating a well-tolerated and effective first line treatment is warranted. In this specific population often there are contra-indications for the use of standard first line drugs like anthracyclines and taxanes due to comorbidities (e.g. cardiac impairment or Peripheral neuropathy). Response rates in first line treatment with taxanes and anthracyclines usually do not exceed 30%. Eribulin has shown a response rate of 29% and a clinical benefit rate (corresponding to the investigators primary endpoint) of 52% in first line, so the investigators expect similar efficacy, but less toxicity. Optimal dose, schedule and tolerability of this drug in the first line setting are unknown in the elderly population. No information on dose modifications in this population is available. Based on the data of eribulin in the first line with higher efficacy in those patients with dose reductions, the SAKK 25/14 trial investigates the reduced starting-dose of eribulin of 1.1mg/m2 for this vulnerable population of elderly patients. Growth factors to maintain a certain dose level of eribulin are not recommended, respecting the international guidelines. SAKK has a tradition in conducting trials in the elderly population, such as SAKK 25/99 in metastatic breast cancer, SAKK 38/08 in aggressive B-cell-Lymphoma, SAKK 41/10 in metastatic colorectal cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer, Adenocarcinoma

Keywords

Eribulin, Breast Cancer, Elderly Patient, Phase II Trial, HER2-neg, adenocarcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

78 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm: Eribulin mesilate

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Eribulin mesilate

Other Intervention Name(s)

Halaven

Intervention Description

Eribulin mesiylate 1.1mg/m2 d1, 8 every 3 weeks until Progressive disease PD

Primary Outcome Measure Information:

Title

Disease Control (DC)

Description

A patient has DC, if she has complete response (CR) or partial response (PR) at any time point during treatment, or if she has stable disease (SD) for at least 24 weeks (according to RECIST v1.1).

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Time to treatment failure (TTF)

Description

Time Frame

at treatment discontinuation (at the latest 5 years after registration)

Title

Objective response (OR)

Description

Time Frame

at treatment discontinuation (at the latest 5 years after registration)

Title

Time to progression (TTP)

Description

Time Frame

at time of progression, death or treatment discontinuation (at the latest 5 years after registration)

Title

Overall survival (OS)

Description

OS is defined as time from registration until death from any cause. Patients not experiencing an event will be censored at the last date they were known to be alive.

Time Frame

at time of death (at the latest 5 years after registration)

Title

Adverse events (AEs)

Description

AEs will be assessed according to NCI CTCAE v4.0.

Time Frame

until 30 days after last dose of treatment and resolution of all related AEs thereafter (at the latest 5 years after registration)

Title

Patient reported neuropathy (PRO Form) and characterization of patients based on cancer-specific geriatric assessment (C-SGA)

Time Frame

at the first follow-up visit (at the latest 5 years after registration)

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient must give written informed consent according to ICH/GCP regulations before registration Histologically or cytologically confirmed locally advanced or metastatic HER2-neg, hormone receptor positive or negative adenocarcinoma of the breast with measurable or evaluable disease according to RECIST 1.1 criteria At least 6 months since last adjuvant/neoadjuvant chemotherapy administration before registration At least 2 weeks since prior radiotherapy or endocrine therapy and complete recovery from these interventions at time of registration Baseline C-SGA and patient-reported outcome (PRO) forms have been completed Female patient at the age of ≥70 years WHO performance status 0-2 Adequate hematological values: hemoglobin ≥80 g/L (transfusions are allowed), neutrophils ≥1.5 x 109/L, platelets ≥ 100 x 109/L Adequate hepatic function: bilirubin ≤1.5 x ULN, AST ≤3 x ULN, alkaline phosphatase (AP) ≤2.5 x ULN (in case of liver metastases ≤5 x ULN or in case of bone metastases ≤10 x ULN) Adequate renal function (calculated creatinine clearance >40 mL/min, according to the formula of Cockcroft-Gault) Exclusion Criteria: Known CNS metastases Previous malignancy within 3 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer Prior chemotherapy for advanced disease Concurrent anticancer treatment or treatment in a clinical trial within 30 days prior to registration. Exception: participation in SAKK 96/12 Palliative irradiation prior to study entry with more than 30% of marrow-bearing bone irradiated Pre-existing neuropathy ≥G2 (according to CTCAE v4.0) at registration Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV (see Appendix 4), unstable angina pectoris, history of myocardial infarction within the last three months, significant arrhythmias, congenital long QT-syndrome) Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information Known hypersensitivity to trial drug or to any component of the trial drug Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes) Psychiatric disorder precluding understanding of trial information, giving informed consent, taking part in the geriatric assessment, or interfering with compliance/with the trial protocol Any familial, sociological or geographical condition potentially hampering proper staging and compliance with the trial protocol

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ursula Hasler-Strub, MD

Organizational Affiliation

Cantonal Hospital of St. Gallen

Official's Role

Study Chair

Facility Information:

Facility Name

Kantonsspital Aarau

City

Aarau

ZIP/Postal Code

CH-5001

Country

Switzerland

Facility Name

Kantonsspital Baden

City

Baden

ZIP/Postal Code

5404

Country

Switzerland

Facility Name

Universitaetsspital-Basel

City

Basel

ZIP/Postal Code

4031

Country

Switzerland

Facility Name

Praxis für ambulante Tumortherapie

City

Basel

ZIP/Postal Code

CH-4052

Country

Switzerland

Facility Name

Istituto Oncologico della Svizzera Italiana

City

Bellinzona

ZIP/Postal Code

6500

Country

Switzerland

Facility Name

Klinik Engeried / Oncocare

City

Bern

ZIP/Postal Code

3012

Country

Switzerland

Facility Name

Inselspital, Bern

City

Bern

ZIP/Postal Code

CH-3010

Country

Switzerland

Facility Name

Spitalzentrum Biel

City

Biel

ZIP/Postal Code

CH-2501

Country

Switzerland

Facility Name

Kantonsspital Graubünden

City

Chur

ZIP/Postal Code

7000

Country

Switzerland

Facility Name

Kantonsspital Frauenfeld / Brustzentrum Thurgau

City

Frauenfeld

ZIP/Postal Code

8501

Country

Switzerland

Facility Name

HFR Fribourg - Hôpital cantonal

City

Fribourg

ZIP/Postal Code

1708

Country

Switzerland

Facility Name

Clinique de Genolier

City

Genolier

ZIP/Postal Code

CH-1272

Country

Switzerland

Facility Name

Centre Hospitalier Universitaire Vaudois

City

Lausanne

ZIP/Postal Code

CH-1011

Country

Switzerland

Facility Name

Clinica Sant'Anna - Oncologia Varini & Calderoni & Christinat

City

Lugano

ZIP/Postal Code

6900

Country

Switzerland

Facility Name

Kantonsspital Luzern

City

Luzerne

ZIP/Postal Code

CH-6000

Country

Switzerland

Facility Name

Onkologie Zentrum Spital Männedorf

City

Männedorf

ZIP/Postal Code

8708

Country

Switzerland

Facility Name

Kantonsspital Olten

City

Olten

ZIP/Postal Code

4600

Country

Switzerland

Facility Name

Rundum Onkologie am Bahnhofpark

City

Sargans

ZIP/Postal Code

7320

Country

Switzerland

Facility Name

Onkologiezentrum Bürgerspital Solothurn

City

Solothurn

ZIP/Postal Code

CH-4500

Country

Switzerland

Facility Name

Onkologiepraxis Dr. med. Isabella Schönenberger

City

St. Gallen

ZIP/Postal Code

9000

Country

Switzerland

Facility Name

Tumorzentrum ZeTUP

City

St. Gallen

ZIP/Postal Code

9006

Country

Switzerland

Facility Name

Kantonsspital - St. Gallen

City

St. Gallen

ZIP/Postal Code

CH-9007

Country

Switzerland

Facility Name

Regionalspital

City

Thun

ZIP/Postal Code

3600

Country

Switzerland

Facility Name

Kantonsspital Winterthur

City

Winterthur

ZIP/Postal Code

8401

Country

Switzerland

Facility Name

Onkozentrum - Klinik im Park

City

Zurich

ZIP/Postal Code

8002

Country

Switzerland

Facility Name

Brust-Zentrum AG Zürich

City

Zürich

ZIP/Postal Code

8005

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

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Eribulin as 1st Line Treatment in Elderly Patients With Advanced Breast Cancer

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