E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically proven metastatic breast cancer. |
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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 |
To investigate the efficacy of 2 doses of ZK 219477 in patients with metastatic breast cancer in progression following a maximum of 2 previous regimen of chemotherapy. Previous chemotherapy must not include taxanes or vinca alkaloids. |
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E.2.2 | Secondary objectives of the trial |
To investigate safety and tolerability of 2 doses of ZK 219477. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Females aged >/= 18 years
2. Histologically proven (at diagnosis), metastatic breast cancer
3. At least 1 unidimensionally measurable lesion (suitable for modRECIST evaluation)
4. Performance status: WHO 0-1
5. Progression of disease following a maximum of two previous steps of chemotherapy, including treatments in an adjuvant or neoadjuvant setting
6. No previous taxane or vinca alkaloid treatment
7. No more than 1 non cytotoxic therapy (biologic agents)
8. No radiotherapy, chemotherapy, or immune/biologic therapy within 3 weeks prior to first dose of ZK 219477
9. Adequate recovery from previous surgery, radiation, and chemotherapy
10. Adequate function of major organs and systems
Hematopoietic: - Hemoglobin >/= 10 g/dL - WBC >/= 3,000/mm3 - Absolute neutrophil count >/= 1,500/mm3 - Platelet count >/= 100,000/mm3
Hepatic: - Bilirubin within normal limits - AST/ALT </= 5 times the upper limit of normal
Renal: - Creatinine </= 2 mg/dL
Cardiovascular: - No New York Heart Association (NYHA) class III or IV heart failure (see Attachment 4) - No unstable angina pectoris - No arrhythmia needing continuous treatment
No other uncontrolled concurrent illness
11. Negative pregnancy test at enrollment (females of childbearing potential only)
12. Agreement to use highly effective contraception methods (intra-uterine contraceptive device [IUCD], condoms, oral contraceptives, or other adequate barrier contraception) in females of child-bearing potential
13. In case the patients participate in the optional PET-Scan substudy: Able to tolerate PET imaging
14. Written informed consent
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E.4 | Principal exclusion criteria |
1. More than 2 previous chemotherapy regimens (including those given in an adjuvant or neo-adjuvant setting)
2. Peripheral neuropathy
3. Any prior treatment with epothilones
4. Use of any investigational drug within 4 weeks before start of study treatment or inadequate recovery from any toxic effects of such therapy
5. Candidacy for curative resection
6. Brain metastases requiring whole-brain irradiation
7. Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix
8. Active infection
9. Breast-feeding
10. Any conditions that in the opinion of the investigator could hamper the compliance with the study protocol
11. In case the patients participate in the optional PET-Scan substudy: Poorly controlled diabetes defined as fasting glucose levels of >200 mg/dL.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with either CR or PR as best overall response |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.2 | Open | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
uncontrolled, open, parallel group comparison of two doses |
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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.8.3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |