E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
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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 efficacy (clinical benefit) of two doses of ZK PRA (25 mg and 100 mg) when administered once daily p.o. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate safety and tolerability - To evaluate the pharmacokinetics of ZK PRA - To evaluate the effect of ZK PRA on quality of life (QoL) - To perform exploratory analysis of biomarkers
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria:
1. Postmenopausal women defined as: - aged >/= 50 years with amenorrhea for at least 12 months or - aged </= 50 years with 6 months of spontaneous amenorrhea and follicle stimulating - hormone (FSH) level within postmenopausal range (> 40 mIU/ml) or - having undergone bilateral oophorectomy
2. Histologically or cytologically confirmed breast cancer
3. Metastatic breast cancer (Stage IV according to UICC – Union internationale Contre Cancer - criteria)
4. Progesterone receptor (PR)-positive tumors
5. Patients must be considered candidates for endocrine therapy (no other therapies for breast cancer are required)
6. Disease progression after first-line endocrine therapy for advanced breast cancer (i.e. with tumor remission or stabilization lasting at least 3 months under endocrine therapy)
7. At least one measurable or non measurable tumor lesion (according to RECIST criteria)
8. WHO Performance status 1 or lower
9. Adequate function of major organs and systems
Hematopoietic: - Hemoglobin: >= 10 g/dL - Absolute neutrophil count: >= 1,500/mm3 - Platelet count: >= 100,000/mm3
Hepatic: - Total bilirubin: <=1.5 times the upper limit of normal - AST/ALT: <=2.5 times the upper limit of normal
Renal: - Creatinine: <=1.5 times the upper limit of normal
Gynecological: - Endometrial thickness (in non-hysterctomised women) ≤ 10 mm double layer An endometrial biopsy needs to be performed if endometrial thickness increases by more than 2 mm compared to baseline or if clinical symptoms of endometrial changes (e.g. vaginal bleeding) occur.
No other uncontrolled concurrent illness
10. Adequate recovery from previous surgery, radiation and chemotherapy
11. Written informed consent
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded:
1. Presence of any of the following conditions: - life-threatening metastatic visceral disease (extensive hepatic involvement) - any metastases to the central nervous system (CNS) - pulmonary lymphangitic metastases involving more than 50% of the lung
2. More than one prior endocrine treatment for advanced breast cancer
3. The following previous treatments should not be excluded: • one first line previous chemotherapy for metastatic disease • combination therapy of 2 endocrine agents (e.g. aromatase inhibitors and anti-estrogen) • previous sequential endocrine treatment with aromatase inhibitors or anti estrogens (if there was no disease progression between the treatments). The following previous treatments should be excluded: • Combination of endocrine therapy with an investigational drug (e.g. anti-angiogenic treatment)
4. Patients with breast cancer HER-2 positive or unknown HER-2 status are not eligible
5. Malignancies or history of prior malignancy other than carcinoma in situ of the cervix or uterus, or basal and squamous cell carcinoma of the skin
6. Intake of CYP3A4 inhibitors less than 2 weeks before start of study treatment
7. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds (ms))
8. A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
9. The use of concomitant medications that prolong the QT/QTc interval
10. Discontinuation of any non endocrine investigational drug therapy 4 weeks or at least 5 half lives before start of treatment (4 weeks for faslodex and 2 weeks for any other endocrine therapy)
11. Expectation that the patient will not be able to complete at least 3 months of therapy
12. Unwillingness or inability to comply with the protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical Benefit (CB): proportion of patients with:
- Complete response (CR) or partial response (PR) at any time point
or
- Stable disease (SD) for 6 months from the start of study treatment
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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 | No |
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 | No |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 4 |
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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In compliance with EU regulations, the ‘end of the study’ is defined as the last patient’s last visit (LPLV).
The 'last patient' is the last patient to complete her EoS or safety follow-up visit, whichever comes 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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |