E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2-negative breast cancer with brain metastases |
cancer du sein HER2 négatif avec métastases cérébrales |
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E.1.1.1 | Medical condition in easily understood language |
brain metastases from HER2-negative breast cancer |
métastases cérébrales secondaires à un cancer du sein HER2 négatif |
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 eribulin for treatment of HER2-negative BCBM |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety of Eribulin in this population.
- Time to WBRT (cohort A and B)
- CNS progression-free survival
- Overall survival
- To assess the change in cognitive function
- Quality of life
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. At least 18 years of age.
2. Life expectancy of 3 months or longer.
3. ECOG performance status of 0, 1, or 2.
4. HER2-negative (IHC 0/1+ or 2+ and in situ hybridization negative) metastatic breast cancer
5. Locally advanced or metastatic breast cancer that have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting unless pa-tients were not suitable for these treatments. (no limit to the number of previous lines of therapy, no need for extracranial disease)
6. At least 2 weeks washout period post chemotherapy, targeted or biologic therapy, or radiation therapy is required prior to study entry
7. Patient with untreated CNS disease or previous SRS/surgery without WBRT (cohorts A and B)
- At least 1 measurable CNS lesion ≥ 10 mm on T1-weighted gadolinium-enhanced MRI, OR
- At least one CNS tumor measuring 5-9 mm in longest diameter, plus one or two addi-tional CNS tumors measuring ≥ 3 mm in longest diameter, for which the sum of the longest diameters is ≥ 10 mm.
8. Patient with progressive disease harboring brain metastases after previous WBRT (cohort C)
- At least 1 measurable CNS lesion ≥ 10 mm on T1-weighted gadolinium-enhanced MRI, OR
- At least one CNS tumor measuring 5-9 mm in longest diameter, plus one or two addi-tional CNS tumors measuring ≥ 3 mm in longest diameter, for which the sum of the longest diameters is ≥ 10 mm.
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E.4 | Principal exclusion criteria |
1. Prior therapy with eribulin.
2. Patients should not have had major surgery or radiotherapy (therapeutic and/or pallia-tive) within 14 days prior to initiation of study treatment, including CNS-directed radia-tion therapy. (Minor procedures, such as tumor biopsy, thoracentesis, or intravenous catheter placement are allowed with no waiting period)
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E.5 End points |
E.5.1 | Primary end point(s) |
Eribulin efficacy will be assessed by estimating CNS objective response rate per RANO-BM criteria. CNS objective response rate will be defined as the rate of patients with a partial response or a complete response as defined by RANO-BM criteria.
Brain MRI will be performed at inclusion and every 6 weeks thereafter during the treatment phase to allow CNS disease assessment according to RANO-BM criteria. CNS disease will be evaluated centrally by trained radiologists and response status will be defined according both radiological and clinical (including steroids use and clinical status) assessments. Tumor response will be confirmed by a second examination performed at least 4 weeks after the criteria for response will be met.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Brain MRI will be performed at inclusion and every 6 weeks thereafter during the treatment phase to allow CNS disease assessment according to RANO-BM criteria. Tumor response will be confirmed by a second examination performed at least 4 weeks after the criteria for response will be met. |
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E.5.2 | Secondary end point(s) |
- Toxicity will be evaluated before every chemotherapy infusion according to NCI CTCAE v5.0 criteria. All treatment-related adverse events will be collected. The rate of grade 3 to 5 adverse events will be analyzed.
- Time to WBRT will be defined as the time from Eribulin initiation to WBRT start.
- CNS progression-free survival will be defined as the time from Eribulin initiation to CNS disease progression according to RANO-BM criteria or death from any cause.
- Overall survival will be defined as the time from Eribulin initiation to death from any cause.
- Cognitive function will be evaluated by self-report Fact-Cog v3.0 questionnaires that will have to be filled every two cycles (before every day 1 infusion).
- Quality of life will be measured by Functional Assessment of Cancer Therapy-Brain Metastasis (FACT-Br v4.0) questionnaire. This questionnaire will be filled every two cycles.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Toxicity and time to WBRT: the time from Eribulin initiation to WBRT start
CNS progression-free survival: the time from Eribulin initiation to CNS disease progression according to RANO-BM criteria or death from any cause
overall survival: the time from Eribulin initiation to death from any cause
Fact-Cog and Fact-Br: every two cycles |
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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 | No |
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |