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

NCT05833919 | Unknown Phase 2

• 1 other identifier: GIM22-ERICA
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 25

Brief 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.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Overall Survival from the date of randomization

  62 months

• Health-related Quality of Life (QoL)

  At screening and then every 8 weeks (including at the time of disease progression/s)

• Disease Control Rate

  62 months

• Post Progression Survival (PPS)

  62 months

Other Outcomes (1)

• Biomarker analysis on patients' blood samples

  Baseline and 62 months

Study Arms (2)

ARM A

EXPERIMENTAL

Second line Eribulin 1.23 mg/m2 i.v. on day 1, 8 every 21 days followed by third line Capecitabine 1250 mg/m2 orally twice per day on days 1 to 14 every 21 days.

Drug: Eribulin Mesylate; Drug: Capecitabine

ARM B

EXPERIMENTAL

Second line Capecitabine 1250 mg/m2 orally twice per day on days 1 to 14 every 21 days; followed by third line Eribulin 1.23 mg/m2 i.v. on day 1, 8 every 21 days.

Drug: Eribulin Mesylate; Drug: Capecitabine

Interventions

Eribulin Mesylate DRUG

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

Also known as: Eribulin

ARM A; ARM B

Capecitabine DRUG

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.

ARM A; ARM B

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Consorzio Oncotech: lead

Study Sites (25)

Fondazione Poliambulanza, Istituto Ospedaliero

Brescia, 25124, Italy

Location

A.R.N.A.S. Garibaldi - P.O. Nesima

Catania, 95122, Italy

Location

A.O. Pugliese-Ciaccio

Catanzaro, 88100, Italy

Location

A.O. S. Croce e Carle

Cuneo, 12100, Italy

Location

Ospedale Civile degli Infermi

Faenza, 48018, Italy

Location

Ospedale Fabrino Spaziani

Frosinone, 03100, Italy

Location

Ospedale Policlinico San Martino

Genova, 16132, Italy

Location

A.O. Ospedale Papardo

Messina, 98158, Italy

Location

AORN dei Colli - Ospedale Monaldi

Napoli, 80131, Italy

Location

Azienda Ospedaliero Universitaria Federico II

Napoli, 80131, Italy

Location

Istituto Nazionale dei Tumori - Fondazione G. Pascale

Napoli, 80131, Italy

Location

Università degli studi della Campania L. Vanvitelli

Napoli, 80131, Italy

Location

P.O. Santa Maria delle Grazie - ASL Napoli 2 Nord

Pozzuoli, 80078, Italy

Location

P.O. San Paolo - ASL Roma 4

Roma, 00053, Italy

Location

Università Campus Biomedico

Roma, 00128, Italy

Location

Policlinico Universitario Tor Vergata

Roma, 00133, Italy

Location

IFO - Istituto Nazionale Tumori Regina Elena - U.O.C. Oncologia Medica 1

Roma, 00144, Italy

Location

IFO - Istituto Nazionale Tumori Regina Elena - U.O.C. Oncologia Medica 2

Roma, 00144, Italy

Location

Ospedale Sandro Pertini - ASL Roma 2

Roma, 00157, Italy

Location

Fondazione Policlinico A. Gemelli

Roma, 00168, Italy

Location

Policlinico Universitario A. Gemelli

Roma, 00168, Italy

Location

Presidio Cassia Sant'Andrea - ASL Roma 1

Roma, 00189, Italy

Location

ASST Lariana - Ospedale Sant'Anna

San Fermo della Battaglia, 22020, Italy

Location

ASUFC P.O. "Santa Maria della Misericordia"

Udine, 33100, Italy

Location

ASST Sette Laghi - Ospedale Di Circolo e Fondazione Macchi

Varese, 21100, Italy

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

eribulin; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Mario R D'Andrea, MD

  UOSD Oncologia, Presidio Ospedaliero San Paolo, Civitavecchia, Rome, Italy

  STUDY CHAIR

• Michelino De Laurentiis, MD

  Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: HER 2 negative MBC patients, who have progressed to a first line chemotherapy for metastatic disease and meet all the inclusion criteria, will be considered eligible for study enrollment. Patients will be randomly allocated using a 1:1 allocation centralized method into the two study arms: ARM A or ARM B. Randomization will be performed with a minimization procedure that will account for the following parameters as strata: * center; * ECOG Performance Status (0-1 vs 2); * previous use of CDK inhibitor (yes vs no); * previous use of bevacizumab (yes vs no); * triple negative breast cancer (yes vs no).

Study Record Dates

• First Submitted: February 1, 2023
• First Posted: April 27, 2023
• Study Start: July 30, 2018
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: April 27, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (25)