E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with HER2 negative, Locally Recurrent or Metastatic Breast Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Patients with breast cells that do not have on their surface the HER2 protein (receptor for the Human epidermal growth factor receptor 2) and that have locally repeated or spread breast cancer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006198 |
E.1.2 | Term | Breast cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of balixafortide + eribulin versus eribulin monotherapy on (i) PFS in the Overall Population and (ii) PFS and objective response rate (ORR) in the 3rd line + population. |
|
E.2.2 | Secondary objectives of the trial |
• To compare the OS between patients in the balixafortide + eribulin treatment arm versus eribulin monotherapy treatment arm. • To compare measures of tumor response between patients in the balixafortide + eribulin treatment arm versus eribulin monotherapy treatment arm. • To evaluate the safety and tolerability of balixafortide + eribulin versus eribulin |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients at least 18 years of age (or according to local regulation) 2. Documented histologically confirmed BC. 3. Metastatic BC currently of stage IV disease by American Joint Committee on Cancer criteria or unresectable locoregionally recurrent BC. 4. Molecular status and prior therapies: a) Molecular Status Eligible patients are, by their patient records and prior therapy, HER2 negative with any ER or PgR status. If a previous record of the HR status is not available, the HR status should be tested locally. HER2 negative (immunohistochemistry [IHC] 0,1 or fluorescence in situ hybridization [FISH] or chromogenic in situ hybridization [CISH] HER2:CEP17 ratio < 2.0); HER2 2+ patients should be ISH/CISH negative. b) Prior Therapies Patients with locally recurrent or metastatic BC who have previously received 1−4 chemotherapeutic regimens for the treatment of locally recurrent or metastatic BC. Unless contra-indicated for safety reasons, prior therapy will have included an anthracycline and a taxane in either the adjuvant or metastatic setting. Patients with HR positive status (ER+ and/or PgR+) must have been treated with at least one line of endocrine therapy and considered by the treating physician not to be a candidate for further endocrine therapy. 5. At least 14 days from the completion of any previous cytotoxic chemotherapy, biological therapy, or any other investigational agent at time of initiation of study medication. Resolution of chemotherapy and radiation therapy related toxicities to Grade 1 or lower severity, except for stable sensory neuropathy Grade 2 or lower and alopecia. 6. Patients must have proved refractory to the most recent chemotherapy, documented by progression on or within six (6) months of therapy. 7. Females of child bearing potential must be willing and able to use highly effective contraception (as described in the protocol) whilst they or their male partners are on this study from randomization until 3 months after the last dose of study medication (Section 5.4.5). Male patients must commit to using an approved form of birth control (including double-barrier contraception [e.g. consistent and correct use of male condom with diaphragm or male condom with cervical cap] or sterilization method) whilst on treatment and for 3 months after the last dose of study medication (Section 5.4.5). 8. ECOG performance status of 0-2. 9. Life expectancy of 3 months or more as per Investigator assessment. 10. Adequate organ function defined at Screening as: a) White blood cell (WBC) ≥3000/mm3. b) Absolute neutrophil count (ANC) ≥1500/mm3. c) Platelets ≥75000/mm3.* * ≥100000/mm3 in France d) Creatinine Clearance ≥30 mL/minute as calculated by the Cockcroft-Gault equation or serum creatinine <1.5x institutional upper limit of normal (ULN). e) Total bilirubin ≤1.5x institutional ULN; aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤3x institutional ULN (for patients with liver metastases, ≤5x ULN). f) Hemoglobin ≥10 g/dL. 11. Patients who have central nervous system involvement if metastases have been treated and are stable for at least 4 weeks after completion of radiation therapy and/or surgery. Stable is defined as the absence of the need for dexamethasone or other corticosteroid therapy, and radiographic confirmation of SD. 12. Patients receiving bone-modifying agents (BMA [bisphosphonates or denosumab]) if BMA was initiated at least 4 weeks prior to the start of study medication. 13. Must be willing and able to comply with the protocol and must understand and sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent document. 14. Affiliation with a National Health Insurance plan (applicable to patients in France only). |
|
E.4 | Principal exclusion criteria |
1. Previously received eribulin. 2. Peripheral neuropathy Grade ≥3. 3. Receipt of prior CXCR4 therapy. 4. Receipt of colony stimulating factors (CSFs) filgrastim, pegfilgrastim, or sargramostim within 14 days prior to time of initiation of study medication. 5. Radiation therapy within 14 days prior to time of initiation of study medication. 6. Severe concurrent illness or psycho-social situation that would limit compliance with study requirements or that, in the Investigator’s opinion, would preclude enrolment. 7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to balixafortide or eribulin, or known intolerance to balixafortide or eribulin. 8. Breast feeding or pregnant, as determined by a serum pregnancy test beta human chorionic gonadotrophin (β-HCG) at Screening and prior to the administration of study medication. 9. Patients with congestive heart failure, electrolyte abnormalities, bradyarrhythmias, known congenital long QT syndrome, QT interval corrected with Fridericia's formula (QTcF) ≥470 msec at baseline in the absence of bundle branch block, or currently taking drugs at known risk of prolonging the QT interval or causing torsades de pointes (including Class Ia and III anti-arrhythmic drugs; see also Appendix 1 Prohibited Medications). Patients with hypokalemia or hypomagnesemia should not be randomized until the hypokalemia or hypomagnesemia is corrected. 10. Patients with a concurrent malignancy or malignancy 2 years prior to randomization with the exception of adequately treated basal and squamous cell carcinoma, non-melanomatous skin cancer, or curatively resected cervical cancer. 11. Persons who have been housed in an institution due to a government or judicial order (applicable to Germany only). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
PFS time (defined as the time from randomization to the first progression or death, as judged by an IRC) is the primary endpoint in the Overall Population. PFS will be analyzed via Cox regression modelling in the intent-to-treat (ITT) population. Patients free from progression and death will be censored at their last follow-up visit. The analysis will be stratified for randomization stratification factors and a fixed effect term will be included for randomized treatment. The hazard ratio will be estimated from the model along with the associated confidence interval (CI) and 2-sided p value. The data will also be displayed using Kaplan- Meier curves and median PFS times will be estimated. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 6 weeks (±7 days) during the first year, and then every 12 weeks (±7 days), thereafter, until Progressed Disease (PD) is documented |
|
E.5.2 | Secondary end point(s) |
OS will be the key secondary efficacy endpoint in the Overall Population. OS will be analyzed in a fashion similar to that described for PFS. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
every 6 weeks (±7 days) during the first year, and then every 12 weeks (±7 days), thereafter, until PD is documented |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker testing in Blood, Plasma and tumor tissue |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Belgium |
Brazil |
Czech Republic |
France |
Germany |
Italy |
Korea, Republic of |
Russian Federation |
Spain |
Taiwan |
Ukraine |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study (study completion) is defined as the date on which all patients have completed the 30-day Safety Follow-up and when the final OS analysis is completed, this is expected to be 2 years after the last patient is enrolled on study. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |