E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormone Receptor Positive Advanced Breast Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072737 |
E.1.2 | Term | Advanced breast cancer |
E.1.2 | System Organ Class | 100000004864 |
|
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 compare the clinical benefit rate of patients treated with fulvestrant 500 mg with the clinical benefit rate of patients treated with anastrozole 1 mg |
|
E.2.2 | Secondary objectives of the trial |
1. To compare the objective response rate of patients treated with fulvestrant 500 mg with the objective response rate of patients treated with anastrozole 1 mg
2. To compare the time to progression of patients treated with fulvestrant 500 mg with the time to progression of patients treated with anastrozole 1 mg
3. To describe the duration of response of patients treated with fulvestrant 500 mg and the duration of response of patients treated with anastrozole 1 mg.
4. To describe the duration of clinical benefit of patients treated with fulvestrant 500 mg and the duration of clinical benefit of patients treated with anastrozole 1 mg.
5. To assess the safety and tolerability of fulvestrant 500mg treatment compared with anastrozole 1 mg. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Provision of written informed consent
2.Histological/cytological confirmation of breast cancer
3.Documented positive hormone receptor status (ER +ve and/or PgR + ve) of primary or metastatic tumour tissue, according to the local laboratory parameters
4.Patients with metastatic or locally advanced disease not amenable to therapy with curative intent:
(a)who have never had hormonal therapy for locoregionally advanced or metastatic disease
and
(b)For patients who have received previous adjuvant or neoadjuvant hormonal treatment, this must have been completed more than 12 months prior to randomisation.
5.Patients fulfilling one of the following criteria:
·Patients with measurable disease as per RECIST criteria. This is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
·Patients with bone lesions, lytic or mixed (lytic + sclerotic), in the absence of measurable disease as defined by RECIST criteria. Bone lesions must be evaluable by plain X-ray, CT or MRI. Patients with lesions identified only on radionucleotide bone scan are not eligible
6. Postmenopausal woman, defined as a woman fulfilling any 1 of the following criteria:
·Age ≥ 60 years
·Age ≥ 45 years with amenorrhoea ≥ 12 months with an intact uterus
·Having undergone a bilateral oophorectomy
·FSH and oestradiol levels in postmenopausal range (utilising ranges from the local laboratory facility)*
* In patients who have previously been treated with an LH-RH analogue, the last depot must have been administered more than 4 months prior to randomisation and menses must not have restarted.
7.WHO performance status 0, 1 or 2. |
|
E.4 | Principal exclusion criteria |
1.Presence of life-threatening metastatic visceral disease, defined as extensive hepatic involvement, or any degree of brain or leptomeningeal involvement (past or present), or symptomatic pulmonary lymphangitic spread. Patients with discrete pulmonary parenchymal metastases are eligible, provided their respiratory function is not significantly compromised as a result of disease
2.Previous systemic therapy for advanced breast cancer.
3.Treatment with a non-approved or experimental drug within 4 weeks before randomisation
4.Current or prior malignancy within previous 3 years (other than breast cancer or adequately treated basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix)
5.Any of the following laboratory values within 3 weeks of randomisation:
·Platelets < 100 x 10 to the power of 9 / L
·Total bilirubin > 1.5 x ULRR**
** Patients with confirmed Gilbert’s syndrome may be included in the study
·ALT or AST > 2.5 x ULRR if no demonstrable liver metastases or > 5 x ULRR in presence of liver metastases
6.History of :
·bleeding diathesis (ie, disseminated intravascular coagulation [DIC], clotting factor deficiency) or
·long-term anticoagulant therapy (other than antiplatelet therapy and low dose warfarin )
7.History of hypersensitivity to active or inactive excipients of fulvestrant, aromatase inhibitors or castor oil
8.Any severe concomitant condition which makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the trial protocol. e.g., uncontrolled cardiac disease or uncontrolled diabetes mellitus. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Clinical benefit (CB) will be obtained for those patients who have a best response (as defined
by RECIST) of either CR, PR or SD as defined by the RECIST criteria. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
For patients with measurable disease at baseline, the RECIST criteria will be used to perform the objective tumour assessments and to categorise best overall objective tumour response for target and non-target lesions. Response will be classified as CR, PR, SD, or progressive disease (PD). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Within 4 weeks of disease assessment. |
|
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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | No |
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 |
Bulgaria |
France |
Italy |
Brazil |
Czech Republic |
Spain |
Poland |
United Kingdom |
United States |
|
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
|
The study will be closed when the last patient discontinues their randomised treatment or approximately 154 (75%) of patients have died, whichever is the later. This is currently estimated to be in 2014. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |