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Randomized phase II study to investigate the efficacy, safety and tolerability of ZK 230211 (25 mg vs. 100 mg) as second-line endocrine therapy for postmenopausal women with hormone receptor-positive metastatic breast cancer

Phase 1
Conditions
Metastatic breast cancer
Registration Number
EUCTR2005-005581-36-GB
Lead Sponsor
Bayer Schering Pharma AG
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Female
Target Recruitment
0
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 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 2 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)
= 5mm double layer

No other uncontrolled concurrent illness

10. Adequate recovery from previous surgery, radiation and chemotherapy

11. Written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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. 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

4. Intake of CYP3A4 inhibitors less than 2 weeks before start of study treatment

5. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds (ms))

6. A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

7. The use of concomitant medications that prolong the QT/QTc interval (

8. Other investigational drug therapies less than 4 weeks before start of study
treatment

9. Expectation that the patient will not be able to complete at least 3 months of
therapy

10. Unwillingness or inability to comply with the protocol

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To evaluate efficacy (clinical benefit) of two doses of ZK PRA (25 mg and 100 mg) when administered once daily p.o.;Secondary Objective: - To evaluate safety and tolerability<br>- To evaluate the pharmacokinetics of ZK PRA<br>- To evaluate the effect of ZK PRA on quality of life (QoL)<br>- To perform exploratory analysis of biomarkers<br>;Primary end point(s): Clinical Benefit (CB): proportion of patients with:<br><br>- Complete response (CR) or partial response (PR) at any time point<br><br>or<br><br>- Stable disease (SD) for 6 months from the start of study treatment<br>
Secondary Outcome Measures
NameTimeMethod
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