| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Hormone receptor positive breast cancer in first relapse after primary treatment of localised tumour, in postmenopausal women. |
|
| 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 primary objective of this study is to estimate time to progression (TTP) at first recurrence in postmenopausal women with hormone receptor positive breast cancer treated with anastrozole monotherapy compared to subjects treated with anastrozole and fulvestrant combination therapy. |
|
| E.2.2 | Secondary objectives of the trial |
-To evaluate the activity of anastrozole alone versus the combination of anastrozole and fulvestrant by estimating the objective response rate (complete response [CR] and partial response [PR]) based on RECIST response criteria.
-to evaluate the clinical benefit (CR+ PR + stable disease [SD])
-to compare the safety and tolerability of anastrozole monotherapy versus anastrozole and fulvestrant combination therapy
-overall survival will be estimated when 60 % of subjects have died |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Provision of written informed consent
2. Postmenopausal female subjects with relapses after primary treatment of localised breast cancer. Postmenopausal women defined as:· Women aged 50 years or over who have not menstruated during 6 months, or who have FSH levels within the post-menopausal range.· Women under the age of 50 years who have not menstruated during 12 months, and who have FSH levels within the post-menopausal range.· Postmenopausal status induced by goserelin 3.6 mg, initiated in the adjuvant setting and not as a treatment for recurrent disease. Treatment with LHRHanalogue must be continued throughout the study period.
3. Histological or cytological confirmed cancer of the breast with locally recurrent
disease, which is unsuitable for local treatment, or metastatic breast cancer. Time
interval from primary surgery to the recurrence/ metastases must be > 8 weeks. It is
recommended that recurrences or metastases are confirmed morphologically,
particularly in case of solitary lesions. Subjects are to be candidates to receive endocrine therapy as their first line systemic treatment for recurrent disease.
Patients who relapse after or while on adjuvant endocrine treatment with tamoxifen
may be included in the study provided they have a recurrence-free interval, I e from
start of their adjuvant tamoxifen until relapse, of more than 12 months.
Patient who relapse while on or after adjuvant cytotoxic chemotherapy may be
included in the trial Patient who relapse after adjuvant therapy with an aromatase inhibitor may be included in the trial provided there is an interval of more than 12 months since stopping this therapy and entry into the current study.
4. Breast cancer must be documented oestrogene and/or PgR positive. Hormone receptor positivity is defined accordingly to routines at each participating laboratory. Cut-off level for positivity shall be predefined for each participating centre. If analyses are done using a quantitative method, a cut-off level for receptor positivety of > 0.05 fmoler/microg. DNA, or > 10 fmol/mg protein is recommended. If analyses are based on immunohistochemistry a cut-off level of > 10% positive tumour cells is
recommended. The receptor determinations should be based on assays of the primary tumor. If such data are unavailable results of receptor analyse of the recurrence may be used instead.Page 25 of 25
5. The breast cancer can be a measurable or non-measurable disease. Chest x-ray and any x-rays and scans for assessment of measurable disease must be performed within 28 days prior to randomisation. Non-measurable disease must be assessed within 42 days prior to randomisation.
Measurable disease: Lesion that can be accurately measured in at least one dimension by 1)medical photograph (skin or oral lesion), palpation, plain x-ray, CT, MRI or other techniquewith longest diameter 2 cm or greater in the axial plane (bone lesions not included), or 2)spiral CT with longest diameter 1 cm or greater. Ultrasound is suitable only for superficial disease (superficial palpable nodes, subcutaneous lesions, thyroid nodules).
Non-measurable disease: Lesions considered to be truly nonmeasurable include the following:bone lesions, ascites, pleural/pericardial effusion, inflammatory breast disease, lymphangitis,cutis/pulmonis, abdominal masses that are not confirmed and followed by imaging techniques and cystic lesions. |
|
| E.4 | Principal exclusion criteria |
1. Previous systemic endocrine therapy for advanced or recurrent breast cancer.
2. Any prior fulvestrant therapy.
3. Premenopausal women.
4. Subjects with known CNS metastases or subjects with only sclerotic bone lesions.
5. Other malignant disease during the past 5 years, except adequately treated and
cured carcinoma in situ cervix uteri or basal cell carcinoma of the skin. Patients
with a diagnosis of malignant disease >5 years ago can be included provided there
is no signs or symtoms of the disease and there is unequivocal evidence that the
current disease represents locally recurrent or metastatic, hormone receptor positive
breast cancer.
6. Subjects not eligible for endocrine treatment for any reason.
7. Currently receiving (and are unwilling to discontinue) oestrogen replacement
therapy.
8. Subjects who have another significant medical or surgical condition, or who require
any other medication, which may interfere with the evaluation of safety and
efficacy of the study treatment. Evidence of severe or uncontrolled systemic disease
(e.g., severe renal or hepatic impairment) or currently unstable or uncompensated
respiratory or cardiac condition at the discretion of the investigator; risk (in the
investigator’s opinion) of transmitting human immunodeficiency virus, hepatitis B
or C, through blood or other bodily fluids.
9. Estimated survival less than three months from the start of study therapy based on clinical judgment.
10. Laboratory results sustained at:
- platelets <100 x 109/l
- prothrombin time (PT) reported as the INR > 1.6
- total bilirubin > 1,5 x ULN
- ALT or AST > 2,5 x ULN if no demonstrable liver disease or > 5 x ULN in
presence of liver metastases
No more than three retests within screening period
11. Subjects who have received any investigational drug/non-approved drug within four weeks of study entry.
12. Subjects who, for whatever reason (e.g. confusion, infirmity, alcohol abuse) are
unlikely to comply with study requirements.
13. History of hypersensitivity to active or inactive excipients of fulvestrant or
anastrozole.
14. Subjects who are on chronic anticoagulant therapy, except for the maintenance of an indwelling venous catheter. This does not include treatment with low-dose
aspirin which is allowed |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Both therapies continues until progression of disease or undue toxicity or withdrawal of consent. |
|
| 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) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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) | Yes |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| 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 |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
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