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

NCT ID: NCT02404506

Last Updated: 2021-09-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-17
• Study Completion Date: 2021-07-22

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.

Conditions

Breast Cancer; Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm: Eribulin mesilate

Group Type: EXPERIMENTAL

Eribulin mesilate

Intervention Type: DRUG

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

Interventions

Eribulin mesilate

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

Intervention Type: DRUG

Other Intervention Names

Halaven

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

• Minimum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ursula Hasler-Strub, MD

Role: STUDY_CHAIR

Cantonal Hospital of St. Gallen

Locations

Kantonsspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Praxis für ambulante Tumortherapie

Basel, , Switzerland

Istituto Oncologico della Svizzera Italiana

Bellinzona, , Switzerland

Klinik Engeried / Oncocare

Bern, , Switzerland

Inselspital, Bern

Bern, , Switzerland

Spitalzentrum Biel

Biel, , Switzerland

Kantonsspital Graubünden

Chur, , Switzerland

Kantonsspital Frauenfeld / Brustzentrum Thurgau

Frauenfeld, , Switzerland

HFR Fribourg - Hôpital cantonal

Fribourg, , Switzerland

Clinique de Genolier

Genolier, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Clinica Sant'Anna - Oncologia Varini & Calderoni & Christinat

Lugano, , Switzerland

Kantonsspital Luzern

Luzerne, , Switzerland

Onkologie Zentrum Spital Männedorf

Männedorf, , Switzerland

Kantonsspital Olten

Olten, , Switzerland

Onkologiepraxis Dr. med. Isabella Schönenberger

Sankt Gallen, , Switzerland

Tumorzentrum ZeTUP

Sankt Gallen, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Rundum Onkologie am Bahnhofpark

Sargans, , Switzerland

Onkologiezentrum Bürgerspital Solothurn

Solothurn, , Switzerland

Regionalspital

Thun, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Onkozentrum - Klinik im Park

Zurich, , Switzerland

Brust-Zentrum AG Zürich

Zurich, , Switzerland

Countries

Switzerland

Other Identifiers

000001310

Identifier Type: OTHER

Identifier Source: secondary_id

SAKK 25/14

Identifier Type: -

Identifier Source: org_study_id