E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This is an open-label, multicenter, randomized controlled, Phase I/II study comparing the time to progressive disease after randomisation in patients treated with 6 cycles of liposomal-encapsulated Doxorubicin (Myocet®) and Cisplatin chemotherapy versus liposomal-encapsulated Doxorubicin and Cisplatin chemotherapy combined with locoregional hyperthermia. |
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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 |
The main objective of this study is to compare the time to progressive disease (TTPD) in a target volume amenable to locoregional hyperthermia in patients treated with liposomal-encapsulated Doxorubicin (Myocet®) and Cisplatin (MC) chemotherapy versus MC-chemotherapy combined with locoregional hyperthermia. The definition of progressive disease will have to be verified by relevant methods of imaging diagnostics according to RECIST criteria.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to compare the following items in the two regimen arms: • Response rate • Survival time after randomisation • Toxicity • Changes in quality of life over time as defined by EORTC QLQ-C30 and QLQ-BR23 questionnaire
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients may be included in the study only if they meet all the following criteria: - Documented metastatic disease other than bone metastases alone - Histopathological confirmed adenocarcinoma of the breast - At least one (2-dimensionally) measurable lesion according to RECIST criteria, applicable to locoregional hyperthermia, which is not intented to receive surgical or radiation therapy - Females 18 years of age - Performance Status ≤2 on ECOG-Scale - Estimated life expectancy of at least 12 weeks - Adequate bone marrow reserve: leucocytes 3.0 x 109/l and platelets 100,000 x 109/l - Serum creatinine level within 1.5 fold of the reference laboratory’s normal range SGOT, SGPT, γ-GT, Alkaline Phosphatase, Bilirubin, Albumin within 2.5 fold of the reference laboratory’s normal range - Left Ventricular Ejection Fraction (LVEF) >50% measured by bidimensional echocardiography - Intention of regular follow up visits for the duration of the study - Ability to understand the nature of the study and to give written informed consent
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study for any of the following reasons:
- For phase-II: More than 3 prior chemotherapy regimens including neo/adjuvant and palliative chemotherapy Note: For phase I, more than 3 prior chemotherapy regimens including neo/adjuvant and palliative chemotherapy are allowed
- Prior anthracycline-containing regimens with more than cumulative dosage of o Epirubicin 600 mg/m2 o Doxorubicin 300 mg/m2 o Mitoxantron 80 mg/m2 - Resistance to anthracycline defined as relapse during or within 12 months after the - second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin) - Pregnancy or breast feeding (in premenopausal women anticonception has to be assured: Intrauterine devices, sterilisation or – only in hormone receptor negative women – oral or subcutaneous non estrogen containing contraception) - Disability to understand the nature of the study and give written consent
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is to evaluate the tumor response rate. The clinical response will be determinated using the RECIST criteria.
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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) | Yes |
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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
treatment without locoregional hyperthermia |
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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 | 5 |
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 | Information not present in EudraCT |
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 | 7 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |