E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Brain metastasis secondary to HER2-negative breast cancer and NSCLC, not previously irradiated and not requiring immediate radiation. |
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E.1.1.1 | Medical condition in easily understood language |
Brain metastasis secondary to HER2-negative breast cancer and non-small cell lung cancer |
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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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006128 |
E.1.2 | Term | Brain metastases |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059282 |
E.1.2 | Term | Metastases to central nervous system |
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 determine if cabazitaxel can induce a reduction in the size of brain metastasis in metastatic HER2-negative breast cancer and NSCLC with BM who were not previously treated with whole brain irradiation or require immediate brain irradiation |
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E.2.2 | Secondary objectives of the trial |
- To determine the effect of cabazitaxel on the time to initiating whole brain irradiation or radiosurgery - To determine the effect of cabazitaxel on the time to developing neurological symptoms - To determine the effect of cabazitaxel on the time to disease progression in the brain - To determine the effect of cabazitaxel on the time to disease progression outside the brain. This will be evaluated separately for the breast and NSCLC cohorts To determine the objective extra-cranial response (if applicable). This will be evaluated separately in the breast and NSCLC cohorts - To determine the safety of cabazitaxel
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed informed consent - Age>18, ECOG 0-1 - Histologically confirmed 1) HER2-negative invasive breast carcinoma or 2) NSCLC - In patients with breast cancer, HER2-negative status by FISH or immunohistochemistry (score 0, or +1). - In patients with breast cancer, known estrogen and progesterone receptor status. - Evidence of measurable disease in the brain (at least 1cm) - Stable or decreasing dosage of steroids for 7 days prior to baseline MRI. - No evidence of (cortical) cognitive impairment as defined by a Mini-Mental Status Exam (MMSE) score ≥ 25/30. - No more than 4 prior lines of systemic chemotherapy in the metastatic setting - Adequate hematopoietic function defined as: • Hemoglobin ≥ 9.0g/dL • Absolute neutrophilic count ≥ 1.5 x 109L • Platelet count ≥ 100 x 109L - Adequate hepatic function defined as: • AST ≤ 2.5 x upper limit of normal (ULN) • ALT ≤ 2.5 x ULN • Total bilirubin ≤ 1.0 x ULN - Adequate renal function defined as serum creatinine ≤ 1.5 x ULN. If creatinine ranges from 1.0 – 1.5 x ULN, creatinine clearance determined by CKD-EPI formula should be calculated and only patients with clearance >60 mL/min are eligible - Adequate contraceptive method in patients with child-bearing potential. |
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E.4 | Principal exclusion criteria |
- History of prior whole brain irradiation - Progressive neurological symptoms requiring immediate brain irradiation - Pregnancy or lactation - History of hypersensitivity reaction to taxanes - History of hypersensitivity to polysorbate 80 containing agents - Current or planned treatment with strong inhibitors or inducers of cytochrome P450. - Less than 3 weeks since the last treatment of chemotherapy, biological therapy, and/or immunotherapy - Leptomeningeal carcinomatosis - Contra-indication to contrast-enhanced MRI
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response defined as a ≥ 50% volumetric reduction of brain lesions in the absence of increasing steroid use, and progressive neurologic symptoms |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Time to whole brain irradiation or radiosurgery - Time to developing neurological symptoms - Time-to-progression in the brain - Time to progression extra-cranial. This will be evaluated separately in the breast and NSCLC cohorts - Objective extra-cranial response rate (if applicable). This will be evaluated separately in the breast and NSCLC cohorts - Toxicity |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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A subject is considered as having completed the study 1 month after the last dose of study drug. Safety follow-up will last 1 month after the last dose of Jevtana or until resolution of all adverse events, whichever is later |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |