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

Sponsor

Swiss Group for Clinical Cancer Research (Other)

Overall Status

Terminated

CT.gov ID

NCT02404506

Collaborator

(none)

Enrollment

Locations

Arm

71.2

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Adenocarcinoma	Drug: Eribulin mesilate	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

78 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 17, 2015

Actual Primary Completion Date :

Dec 30, 2020

Actual Study Completion Date :

Jul 22, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm: Eribulin mesilate	Drug: Eribulin mesilate Eribulin mesiylate 1.1mg/m2 d1, 8 every 3 weeks until Progressive disease PD Other Names: Halaven

Arm

Intervention/Treatment

Experimental: Arm: Eribulin mesilate

Drug: Eribulin mesilate

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

Other Names:

Halaven

Outcome Measures

Primary Outcome Measures

Disease Control (DC) [24 weeks]
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) [at treatment discontinuation (at the latest 5 years after registration)]
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) [at treatment discontinuation (at the latest 5 years after registration)]
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) [at time of progression, death or treatment discontinuation (at the latest 5 years after registration)]
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) [at time of death (at the latest 5 years after registration)]
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) [until 30 days after last dose of treatment and resolution of all related AEs thereafter (at the latest 5 years after registration)]
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) [at the first follow-up visit (at the latest 5 years after registration)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

Female

Accepts 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Kantonsspital Aarau	Aarau	Switzerland	CH-5001
2	Kantonsspital Baden	Baden	Switzerland	5404
3	Universitaetsspital-Basel	Basel	Switzerland	4031
4	Praxis für ambulante Tumortherapie	Basel	Switzerland	CH-4052
5	Istituto Oncologico della Svizzera Italiana	Bellinzona	Switzerland	6500
6	Klinik Engeried / Oncocare	Bern	Switzerland	3012
7	Inselspital, Bern	Bern	Switzerland	CH-3010
8	Spitalzentrum Biel	Biel	Switzerland	CH-2501
9	Kantonsspital Graubünden	Chur	Switzerland	7000
10	Kantonsspital Frauenfeld / Brustzentrum Thurgau	Frauenfeld	Switzerland	8501
11	HFR Fribourg - Hôpital cantonal	Fribourg	Switzerland	1708
12	Clinique de Genolier	Genolier	Switzerland	CH-1272
13	Centre Hospitalier Universitaire Vaudois	Lausanne	Switzerland	CH-1011
14	Clinica Sant'Anna - Oncologia Varini & Calderoni & Christinat	Lugano	Switzerland	6900
15	Kantonsspital Luzern	Luzerne	Switzerland	CH-6000
16	Onkologie Zentrum Spital Männedorf	Männedorf	Switzerland	8708
17	Kantonsspital Olten	Olten	Switzerland	4600
18	Rundum Onkologie am Bahnhofpark	Sargans	Switzerland	7320
19	Onkologiezentrum Bürgerspital Solothurn	Solothurn	Switzerland	CH-4500
20	Onkologiepraxis Dr. med. Isabella Schönenberger	St. Gallen	Switzerland	9000
21	Tumorzentrum ZeTUP	St. Gallen	Switzerland	9006
22	Kantonsspital - St. Gallen	St. Gallen	Switzerland	CH-9007
23	Regionalspital	Thun	Switzerland	3600
24	Kantonsspital Winterthur	Winterthur	Switzerland	8401
25	Onkozentrum - Klinik im Park	Zurich	Switzerland	8002
26	Brust-Zentrum AG Zürich	Zürich	Switzerland	8005