Second Line ERIbulin Followed by CApecitabine or the Reverse Sequence in HER2-negative Metastatic Breast Cancer Patients

Metastatic Breast Cancer Clinical Trial

Official title:

Second Line ERIbulin Followed by CApecitabine or the Reverse Sequence in HER2-negative Metastatic Breast Cancer (MBC) Patients: a Randomized Phase II Study - ERICA Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05833919
• Other study ID #: GIM22-ERICA
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 30, 2018
• Est. completion date: July 2023

Study information

• Verified date: April 2023
• Source: Consorzio Oncotech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

GIM22-ERICA is a clinical trial investigating the efficacy of two different strategies in HER2 negative MBC treatment. The study will include MBC patients with histologically documented HER2 negative disease, who have progressed to one prior regimen for metastatic disease and are eligible for a second-line chemotherapy with either eribulin or capecitabine.

This study design should answer to different questions:

• What is the correct placement of Eribulin in the context of a long term treatment strategy?

• Is an early use of Eribulin the best approach for MBC pts treatment?

• May early use of Eribulin impact on subsequent treatment outcomes?

The correlated biomarkers analysis, evaluating angiogenic, epithelial and mesenchymal markers should confirm the results observed in preclinical studies ad support the clinical findings. Liquid biopsies and ctDNA evaluation could help to monitor the course of the disease and to identify novel biomarkers of drug resistance.

Description:

Patients who are considered eligible for the study treatment, will be randomly allocated within the two study arms.

ARM A:

• Second line Eribulin 1.23 mg/m2 i.v. on day 1, 8 every 21 days

• third line Capecitabine 1250 mg/m2 orally twice per day on days 1 to 14 every 21 days

ARM B:

• Second line Capecitabine 1250 mg/m2 orally twice per day on days 1 to 14 every 21 days

• Third line Eribulin 1.23 mg/m2 i.v. on day 1, 8 every 21 days

Study treatment will be continued until disease progression, death, unacceptable toxicity, Investigator's decision or patient refusal of further treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 122
• Est. completion date: July 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent (both for clinical and blood biomarker study)

• Histological diagnosis of HER2 negative MBC

• Females = 18 years

• Measurable disease (according RECIST criteria version 1.1)

• Prior Anthracyclines and Taxanes in either (neo-) adjuvant or metastatic setting, unless the patient was not suitable for one of these treatments

• 1 prior cytotoxic regimen for advanced or MBC (not including adjuvant or neo-adjuvant therapy). Patients with no prior cytotoxic regimens for advanced or metastatic disease will only be allowed if they relapsed during or within 6 months of (neo-) adjuvant cytotoxic therapy that included anathracyclines and/or taxanes (see prior criteria);

• Prior hormonotherapy and Cyclines inhibitors are allowed, so as indicated in the international guidelines for the management of hormone positive breast cancer (ER and/or PR positive);

• ECOG Performance Status = 2

• Absence of angina or heart failure or infarction within 12 months from inclusion

• Adequate bone marrow and organ function as follows (haemoglobin =9.0 g/dl; absolute neutrophil count = 1.5x103/mm3; plateled count = 100x103/mm3; bilirubin levels = 1.5 times Upper Limits of Normal

• biliary stenting is allowed to resolve obstruction - Serum Transaminase level = 2.5 times ULN; serum creatinine = 1.5 times ULN;

• Life expectancy of at least 12 weeks;

• If women of childbearing potential (WOCBP) age: effective contraceptive measures must be used during the study treatment period and up to 3 months after the last dose of study drug.

Exclusion Criteria:

• Unability to give informed consent

• Absence of measurable disease

• Concurrent active malignancies (except of in situ carcinoma of the cervix and inactive non-melanoma skin cancer)

• Current active infection;

• Serious pre-existing medical conditions or serious concomitant diseases;

• systemic disorders that would compromise the safety of the patient or her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris, or a clinically significant history of cardiac disease or uncontrolled diabetes mellitus);

• Known immunodeficiency virus infection;

• Pregnant or breastfeeding women

• Unable to undergo medical test for geographical, social or psychological reason;

• Active or symptomatic brain metastases;

• Known complete Dihydropyrimidine dehydrogenase (DPD) deficiency (phenotype and/or genotype testing, according to applicable national guidelines, prior to the initiation of treatment with Capecitabine is recommended)

• Recent or concomitant treatment with brivudine (there must be at least a 4-week waiting period between end of treatment with brivudine and start of capecitabine therapy).

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Eribulin Mesylate
The dose of Eribulin as the ready to use solution is 1.23 mg/m2 which should be administered intravenously over 2 to 5 minutes on Days 1 and 8 of every 21-day cycle. The amount of Eribulin required (calculated above) will be withdrawn from the appropriate number of vials into a syringe. This may be injected directly as an IV bolus over 2-5 minutes or diluted in up to 100 ml 0.9% sodium chloride (NaCl) for IV infusion over 2-5 minutes. The dose of Eribulin may be reduced or discontinued during any cycle in accordance with the toxicity modifications described in this chapter. Toxicities will be managed by treatment interruption and dose reduction. Once the dose has been reduced, it cannot be increased at a later date
• Capecitabine
Capecitabine use in breast cancer is registered as monotherapy in advanced breast cancer after failure of a taxane- and anthracycline-containing chemotherapy or for patients for whom an anthracycline is contraindicated. Capecitabine is available in tablets of 150 and 500 mg. The recommended dose as a single agent is 1,250 mg/m2 b.i.d. (twice daily) for 14 days repeated on day 22. The tablets should be swallowed with water within 30 minutes after a meal. Caution is recommended in patients with ischemic heart disease or coronary artery disease and/or in therapy with sorivudine and analogs, coumarins, and phenytoin.

Locations

Country	Name	City	State
Italy	Fondazione Poliambulanza, Istituto Ospedaliero	Brescia
Italy	A.R.N.A.S. Garibaldi - P.O. Nesima	Catania
Italy	A.O. Pugliese-Ciaccio	Catanzaro
Italy	A.O. S. Croce e Carle	Cuneo
Italy	Ospedale Civile degli Infermi	Faenza
Italy	Ospedale Fabrino Spaziani	Frosinone
Italy	Ospedale Policlinico San Martino	Genova
Italy	A.O. Ospedale Papardo	Messina
Italy	AORN dei Colli - Ospedale Monaldi	Napoli
Italy	Azienda Ospedaliero Universitaria Federico II	Napoli
Italy	Istituto Nazionale dei Tumori - Fondazione G. Pascale	Napoli
Italy	Università degli studi della Campania L. Vanvitelli	Napoli
Italy	P.O. Santa Maria delle Grazie - ASL Napoli 2 Nord	Pozzuoli
Italy	Fondazione Policlinico A. Gemelli	Roma
Italy	IFO - Istituto Nazionale Tumori Regina Elena - U.O.C. Oncologia Medica 1	Roma
Italy	IFO - Istituto Nazionale Tumori Regina Elena - U.O.C. Oncologia Medica 2	Roma
Italy	Ospedale Sandro Pertini - ASL Roma 2	Roma
Italy	P.O. San Paolo - ASL Roma 4	Roma
Italy	Policlinico Universitario A. Gemelli	Roma
Italy	Policlinico Universitario Tor Vergata	Roma
Italy	Presidio Cassia Sant'Andrea - ASL Roma 1	Roma
Italy	Università Campus Biomedico	Roma
Italy	ASST Lariana - Ospedale Sant'Anna	San Fermo Della Battaglia
Italy	ASUFC P.O. "Santa Maria della Misericordia"	Udine
Italy	ASST Sette Laghi - Ospedale Di Circolo e Fondazione Macchi	Varese

Sponsors (1)

Lead Sponsor	Collaborator
Consorzio Oncotech

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarker analysis on patients' blood samples	Tumor Circulating DNA (ctDNA); Angiogenetic markers (VEGF, bFGF); EMT biomarkers (E- Cadherin, N-Cadherin, Vimentin, TGF-beta); Leukocyte-lymphocyte subpopulations; Cytokines	Baseline and 62 months
Primary	Total Progression Free Survival (PFS-T)	Total-progression-free survival (PFS-T) is defined as the time elapsed between randomization and the first event among the following: the date of progression after the second treatment on study -whichever the second treatment will be according to intention-to-treat (eventual departures from treatments planned in the protocol will be described); the date of death if death occurs before second progression; Patients who are alive and who do not fall into any of the above categories at the end of the study will be censored on the date of the last information on vital status.	62 months
Secondary	Overall Survival from the date of randomization	This is defined as the time elapsed from the first day of 2nd line therapy and death	62 months
Secondary	Health-related Quality of Life (QoL)	Assessment will be performed by using EORTC QoL questionnaires (QlQ C30 and specific EORTC QlQ BR23)	At screening and then every 8 weeks (including at the time of disease progression/s)
Secondary	Disease Control Rate	Disease Control Rate (DCR: proportion of patients obtaining complete response or partial response or stable disease >= 6 months): in second line; In third line; In second and/or third line.	62 months
Secondary	Post Progression Survival (PPS)	This is defined as the time elapsed from disease progression after 3rd line of therapy and death;	62 months