E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
newly diagnosed estrogen receptor positive HER2 negative breast
cancer scheduled for surgical treatment |
|
E.1.1.1 | Medical condition in easily understood language |
newly diagnosed breast cancer |
|
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 | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10083234 |
E.1.2 | Term | Hormone receptor positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 explore the ER PD effects of AZD9833 between pre- and on-treatment tumour samples in women with early breast cancer after AZD9833 treatment. |
|
E.2.2 | Secondary objectives of the trial |
1. To explore the PgR and Ki-67 PD effects of AZD9833 between pre- and on-treatment tumour samples in women with early breast cancer after AZD9833 and fulvestrant treatment (if applicable)
2. To evaluate the safety and tolerability of AZD9833 in this patient population.
3. To evaluate the PK of AZD9833 in this patient population. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 Provision of written informed consent prior to study entry
2 Female patients aged at least 18 years
3 Post-menopausal status defined as meeting at least one of the following criteria:
(a) Have undergone a bilateral oophorectomy
(b) Age ≥ 60 years
(c) Age ≥ 50 and < 60 years and with cessation of menses ≥ 12 months and FSH and oestradiol levels in the post-menopausal range and with an intact uterus in the absence of oral contraception or hormone replacement therapy prior to the diagnosis of breast cancer
4 Pre-menopausal status (Stage 2 only) defined as patients who are naturally pre menopausal (i.e. without concurrent ovarian suppression)
(a) Women of childbearing potential must:
(i) Not be breastfeeding
(ii) Have a negative pregnancy test prior to the start of dosing
(iii) Agree to use one highly effective barrier method of contraception from the time of screening until 4 weeks after discontinuing study treatment.
5 Female patients with newly diagnosed primary breast cancer scheduled to undergo treatment with curative intent by surgery and irrespective of clinical node status
6 Histologically confirmed invasive breast cancer involving a palpable tumour of any size, or a tumour with an ultrasound assessed diameter of ≥ 1.0 cm
7 Patients with adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 3 months can be considered for the study
8 According to the local laboratory patients must have:
(a) ER positive breast cancer
(b) HER2-negative breast cancer
9 ECOG performance status 0 to 1 |
|
E.4 | Principal exclusion criteria |
1 Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments)
2 Intervention with any of the following:
(a) Use of sex-hormone-containing drugs within 6 months prior to the first dose of study treatment
(b) Medications or herbal supplements known to be strong inhibitors/inducers of CYP3A4/5, sensitive CYP2B6 substrates and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index
(c) Drugs that are known to prolong QT and have a known risk of torsades de pointes
3 Inflammatory breast cancer
4 Any evidence of severe or uncontrolled systemic diseases which in the investigator’s opinion makes it undesirable for the patient to participate in the study.
5 Any of the following cardiovascular criteria: Mean resting QTcF > 470 msec; resting heart rate of < 50 bpm; any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG; any factors that increase the risk of QTc prolongation or risk of arrhythmic events; known left ventricular ejection fraction < 50%; significant cardiovascular procedure or event within the last 6 months; uncontrolled hypertension or symptomatic hypotension
6 Inadequate bone marrow reserve or organ function
7 Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9833
8 History of hypersensitivity to active or inactive excipients of AZD9833, or fulvestrant (stage 2 only)
9 Previous randomisation in the present study
10 Judgement by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Change from baseline in ER expression between pre and on-treatment tumour samples measured by IHC. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline to day of biopsy |
|
E.5.2 | Secondary end point(s) |
1. Change from baseline in PgR expression between pre and on-treatment tumour samples measured by IHC.
Change from baseline in Ki-67 labelling index between pre and on-treatment tumour samples measured by IHC.
2. Frequency and severity of adverse events (AEs)/Serious adverse events (SAEs).
Vital signs, electrocardiograms (ECGs).
3. Plasma concentrations of AZD9833 on the biopsy day.
. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline to day of biopsy
2. Screening to end of safety follow up visit
3. Day of on-treatment biopsy |
|
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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 7 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Georgia |
Mexico |
United Kingdom |
|
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 end of the study is defined as the last expected visit/contact of the last patient undergoing the study. |
|
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 | 10 |
E.8.9.1 | In the Member State concerned days | 13 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |