E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chemorefractory liver metastases from breast carcinoma |
chemorefractaire levermetastasen van borstcarcinoma |
|
E.1.1.1 | Medical condition in easily understood language |
breast cancer spread to the liver |
borstkanker uitgezaaid naar de lever |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
1. Assessment of systemic toxicity according to the CTC4.0 criteria (http://ctep.info.nih.gov/reporting/ctc.html)
2. Partial response: Changes in tumor volume (RECIST-criteria) and vascularisation/tumor necrosis before versus after chemo-embolization, analysed by MR imaging including perfusion and diffusion-weighted imaging, as a surrogate for survival
3. Time to progression in the liver |
|
E.2.2 | Secondary objectives of the trial |
1. Correlation of perfusion and diffusion weighted images and assessment of the value of diffusion imaging in predicting outcome of transarterial Y90 infusion followed by transarterial MMC chemoinfusion for liver metastases.
2. Overall survival |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Histologically confirmed diagnosis of breast cancer
Radiological evidence of liver metastases
Liver-only or liver predominant disease
Progressive under (multi-line) systemic chemotherapy
Progressive under hormonotherapy for hor+ patients.
Patients scheduled for mitomycine chemoinfusion
Liver/lung shunt < 20% as determined by the Tc99-scan
Age older than 18 years
Karnovski >=70
Written informed consent |
|
E.4 | Principal exclusion criteria |
. Karnovsky < 70
. Biochemical evidence of severe haematological toxicity and liver function test disturbances (Bilirubine > 1.5; AST/ALT > 2.5 fold normal range; Creatinine > 1.2 upper normal limit; GFR (glomerular filtration rate) < 60)
. Neutrophiles < 1000/ml
. Thrombocytes < 100.000
. Liver/lung shunt > 20% as determined by the Tc99-scan
. Allergy to contrast media
. Intake of oral anticoagulation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Assessment of systemic toxicity according to the CTC4.0 criteria (http://ctep.info.nih.gov/reporting/ctc.html)
2. Partial response: Changes in tumor volume (RECIST-criteria) and vascularisation/tumor necrosis before versus after chemo-embolization, analysed by MR imaging including perfusion and diffusion-weighted imaging, as a surrogate for survival
3. Time to progression in the liver
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
week -2
week 1
week 6-10
week 14
week 18
week 22-26-30 |
week -2
week 1
week 6-10
week 14
week 18
week 22-26-30 |
|
E.5.2 | Secondary end point(s) |
1. Correlation of perfusion and diffusion weighted images and assessment of the value of diffusion imaging in predicting outcome of transarterial Y90 infusion followed by transarterial MMC chemoinfusion for liver metastases.
2. Overall survival |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
week -2
week 1
week 6-10
week 14
week 18
week 22-26-30 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
toenemende doses (4 studiecohorten) |
increasing doses (4 study cohorts) |
|
E.8.2.4 | Number of treatment arms in the trial | 4 |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |