Luminal Metastatic Breast Cancer MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864 MedDRA version: 20.1 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: HALAVEN
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ERIBULIN
CAS Number: 253128-41-5
Concentration unit
Sponsors
Medica Scientia Innovation Research (MEDSIR)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible for inclusion only if they meet ALL of the following criteria: 1. Patients have been informed about the nature of study, and have agreed to participate in the study, and signed the informed consent approved by the institution’s independent ethical committee/institutional review board. 2. Female patients over 18 years of age. 3. Patients with a histologically confirmed diagnosis of ER-positive and/or PR-positive breast cancer by local laboratory. 4. Patients with HER2-negative breast cancer through in situ hybridization test (fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], or silver enhanced in situ hybridization [SISH]) or negative immunohistochemical status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing. 5. Unresectable locally advanced or metastatic breast cancer. 6. Confirmed disease progression while in the last aromatase inhibition- containing regimen in the metastatic setting (Note: not necessarily in the treatment line immediately prior to study entry) or within 6 months from last AI dose in the adjuvant setting. Treatment with prior CDK4/6 or mTOR inhibitor therapy is allowed. 7. At least one taxane or anthracycline regimen in either the adjuvant or the neoadjuvant setting. 8. Patients with no prior line of chemotherapy in the metastatic setting. 9. At least 1 and up to 3 prior lines of endocrine therapy in the metastatic setting (except for patients progressing during the adjuvant setting or before 6 months after completing adjuvant endocrine therapy). 10. Eastern Cooperative Oncology Group (ECOG) score 0 or 1. 11. Patients have adequate bone marrow and organ function as defined by the following laboratory values: -Absolute neutrophil count (ANC) = 1.5 x 109 /L. -Platelets = 100 x 109 /L. -Hemoglobin = 9 g/dL. -Sodium, potassium, calcium (corrected for serum albumin), and magnesium within normal limits for the institution. -Adequate renal function as evidenced by calculated creatinine clearance =50 mL/min per the Cockcroft and Gault formula: Cr.Cl.= 0.85 * ((140 – Age years) / (SerumCreat mg/dL)) * (Weight Kg / 72). -Adequate liver function as evidenced by bilirubin =1.5 times the upper limit of normal (ULN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =3×ULN (in the case of liver metastases =5×ULN). 12. Patients must have measurable disease (according to RECIST criteria v.1.1). 13. Premenopausal and postmenopausal women. Premenopausal women must be treated, with LHRH analogues for at least 28 days (if shorter LHRH treatment period, post-menopausal estrogen levels must be confirmed on laboratory assessments) prior to study entry. Premenopausal or postmenopausal status should have been established before starting the previous treatment with an AI +/- LHRH analogue based on the following classification: • Postmenopausal status is defined as either: a) Prior bilateral oophorectomy or b) Age > 60 years or c) Age < 60 years and amenorrheic for 12 months in the abs
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if they meet ANY of the following criteria: 1. Have received radiation therapy or limited-field palliative radiotherapy within two weeks prior to Cycle 1, Day 1, or patients who have not recovered from radiotherapy-related toxicities to baseline or grade £ 1 (except alopecia) and/or from whom =25% of the bone marrow has been previously irradiated. 2. Have received prior chemotherapy for locally advanced or metastatic disease. 3. Have peripheral neuropathy grade 2 or greater. 4. QTc >480 msec on basal assessments, history of congenital or personal history of long QT syndrome, Brugada syndrome, or Torsade de Pointes (TdP), or uncontrolled electrolyte disorders 5. Child-bearing potential women not using highly effective methods of contraception (contraception should continue during dosing and up to 90 days after study drugs discontinuation). 6. Known hypersensitivity to eribulin, endocrine therapy or its excipients. 7. Other malignancies within the previous two years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of cervix or breast. 8. Known uncontrolled metastases to the central nervous system (CNS) or any progressing CNS disease. (Note: Known brain metastases are considered active, if brain imaging during screening demonstrates progression of existing metastases and/or appearance of new lesions compared to brain imaging performed at least four weeks earlier and/or neurological symptoms attributed to brain metastases have not returned to baseline and/or steroids were used for brain metastases within 28 days of randomization) 9. Have a serious concomitant systemic disorder (e.g. active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator) 10. Major surgical procedure (defined as requiring general anaesthesia) or significant traumatic injury within 28 days prior to randomization, or patients who have not recovered from the side effects of any major surgery, or patients that may require major surgery during the course of the study. 11. Have received any anti-cancer biology or investigational treatment within 30 days prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary endpoint is the overall response rate (ORR) in the arm corresponding to the patients treated with eribulin in combination with aromatase inhibitor therapy (eribulin+ET arm), based on local investigator’s assessment according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria v. 1.1;Timepoint(s) of evaluation of this end point: Time from randomization to disease progression; Secondary Objective: • To characterize the progression-free survival (PFS) of eribulin alone and in combination with endocrine therapy. • To characterize progression-free survival-2 of eribulin alone and in combination with endocrine therapy. • To evaluate the overall response rate (ORR) of eribulin alone. • To evaluate the duration of response (DOR) of eribulin alone and in combination with endocrine therapy. • To evaluate the clinical benefit rate (CBR) of eribulin alone and in combination with endocrine therapy. • To evaluate overall survival (OS) in patients treated with eribulin alone and in combination with endocrine therapy. • To evaluate the change in Maximum Tumor shrinkage in patients treated with eribulin alone and in combination with endocrine therapy. • To evaluate the safety, tolerability and toxicity profile of endocrine therapy in combination with eribulin. ;Primary end point(s): The overall response rate (ORR) in the eribulin + ET arms, defined as the proportion of patients with best overall response of confirmed complete response or partial response based on local investigator’s assessment according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria v. 1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • The progression-free survival (PFS) for patients treated with endocrine therapy alone or in combination with eribulin is defined as the time from randomization until death by any cause or objective tumor progression based on local investigator’s assessment according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria v. 1.1. • The PFS-2, in the eribulin and the eribulin + ET arms, defined as the time from the randomization to the second disease progression or death, i.e., PFS after the next line of treatment, based on local investigator’s assessment according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria v. 1.1. • The overall response rate (ORR) in the eribulin arm, defined as the proportion of patients with best overall response of confirmed complete response or partial response based on local investigator’s assessment according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria v. 1.11. • The duration of response (DOR) in the eribulin and the eribulin + ET arms, defined as the time from the start of the treatment to disease progression based on local investigator’s assessment according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria v. 1.1. • The clinical benefit rate (CBR) in the eribulin and the eribulin + ET arms, defined as the proportion of patients with no disease progression after 6 months of therapy, based on local investigator’s assessment according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria v. 1.1. • The overall survival (OS) in the eribulin and the eribulin + ET arms, defined as the length of time that patients remain alive from the start of treatment (OS will be collected at the end of the study). • Maximum Tumor shrinkage, defined as the percentage of tumor shrinkage from baseline (obtained from the sum of the la | — |
Countries
Spain
Contacts
Public ContactNoemí López
Medica Scientia Innovation Research (MEDSIR)
Outcome results
None listed