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

NCT ID: NCT05833919

Last Updated: 2023-04-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-30
• Study Completion Date: 2023-07-31

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.

Detailed 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.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ARM A

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.

Group Type: EXPERIMENTAL

Eribulin Mesylate

Intervention Type: 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

Capecitabine

Intervention Type: 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 B

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.

Group Type: EXPERIMENTAL

Eribulin Mesylate

Intervention Type: 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

Capecitabine

Intervention Type: 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.

Interventions

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Eribulin

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Consorzio Oncotech

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mario R D'Andrea, MD

Role: STUDY_CHAIR

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

Michelino De Laurentiis, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

P.O. San Paolo - ASL Roma 4

Roma, , Italy

Università Campus Biomedico

Roma, , Italy

Policlinico Universitario Tor Vergata

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

Fondazione Policlinico A. Gemelli

Roma, , Italy

Policlinico Universitario A. Gemelli

Roma, , Italy

Presidio Cassia Sant'Andrea - ASL Roma 1

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, , Italy

Countries

Italy

Other Identifiers

GIM22-ERICA

Identifier Type: -

Identifier Source: org_study_id