E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
oestrogen receptor, androgen receptor positive early breast cancer |
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E.1.1.1 | Medical condition in easily understood language |
Breast cancer which is positive for the hormone receptor estrogen and the androgen receptor in early breast cancer |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070575 |
E.1.2 | Term | Estrogen receptor positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070577 |
E.1.2 | Term | Oestrogen receptor positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
the primary objective in this study is to see the response to enobosarm as measured by changes in Ki67 proliferation index after 14 days of treatment in ER positive, AR positive early breast cancer |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives in this study are: 1. Changes in pro-apoptotic marker cleaved caspase 3 after 2 weeks of treatment 2. Changes in expression by immunohistochemistry of PSA, Gross Cystic Disease Fluid Proteins (GCDFP)-24 &-15; PgR, GREB1 after 2 weeks of treatment 3. Changes in circulating steroidogenic hormones & Prostrate Specific Antigen (PSA) 4. Safety and tolerability in terms of: • Occurance of grade 3+ toxicity classified by NCI-CTCAE v4.0. • Occurrence of serious adverse events • Withdrawal from trial treatment due to toxicity • Experience of delay to scheduled surgery
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•16 years of age or older •Histologically confirmed ER+ve breast cancer (Allred ≥3) •AR+ve breast cancer (defined as ≥10% nuclear AR staining by immunohistochemistry)* •Any HER2 status •Tumour measuring ≥14mm in longest diameter by ultrasound (US) examination •Postmenopausal women as defined by one of the following criteria: o Amenorrhoea >12 months at the time of diagnosis and an intact uterus, with FSH and estradiol in the postmenopausal ranges o Prior bilateral oophorectomy o FSH and estradiol levels within the postmenopausal range (as per local practice) in women aged <55 years who have undergone hysterectomy •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 •Adequate renal function defined by a serum creatinine ≤1.5 x ULN. Adequate liver function defined by total bilirubin ≤ 1.5 ULN (patients with Gilbert’s Syndrome exempted), either ALT or AST ≤1.5 ULN and ALP ≤1.5 ULN •Written informed consent, able to comply with treatment and follow up •Able to comply with treatment and follow up
*Immunohistochemistry (IHC) for AR: This will be initially performed by all contributing centres, all of who are CPA accredited laboratories and take part in the national external quality assessment service (NEQAS) IHC assessment schemes. ALL AR IHC will be subsequently be reviewed centrally by the trial pathologists. Ethical permission will be sort of perform prospective AR testing of all ER+ postmenopausal breast cancer, with only those patients with AR+ tumours being approached for study entry in the clinic.
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E.4 | Principal exclusion criteria |
•Inoperable breast cancer •Inflammatory tumours •Evidence of metastatic disease •Any history of invasive malignancy within 5 years of starting study treatment (other than adequately treated basal cell carcinoma or squamous cell carcinoma of the skin and cervical carcinoma in situ) •Evidence of bleeding diathesis •Prior endocrine therapy of chemotherapy for breast cancer •Concomitant use (defined as use within 12 weeks prior to entry) of HRT or any other oestrogen-containing medication or supplement (including vaginal oestrogens and phytoestrogens) •Previous use of oestrogen implants at ANY time •Uncontrolled abnormalities of serum potassium, sodium, calcium or magnesium levels •Evidence of uncontrolled active infection •Evidence of significant medical condition or laboratory finding which, in the opinion of the investigator, makes it undesirable for the patient to participate in the trial •Participation in a clinical trial of an IMP in the last 30 days
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is the change in Ki67 score after 14 days of treatment from baseline (day 1) to surgery (day 14 +4) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Samples will be taken at baseline and after 14 (+4) days of treatment (ending the day before or the day of surgery). |
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E.5.2 | Secondary end point(s) |
•Changes in pro-apoptotic marker cleaved caspase 3 after 2 weeks of treatment •Changes in expression by immunohistochemistry of PSA, Gross Cystic Disease Fluid Proteins (GCDFP)-24 &-15; PgR, GREB1 after 2 weeks of treatment •Changes in circulating steroidogenic hormones & Prostrate Specific Antigen (PSA) •Safety and tolerability in terms of: o Occurrence of grade 3+ toxicity classified by NCI-CTCAE v4.0. o Occurrence of serious adverse events o Withdrawal from trial treatment due to toxicity o Experience of delay to scheduled surgery
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline 14 (+4) days of 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 | 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 | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
control arm - "treatment as usual" |
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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 | 9 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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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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 | 2 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 1 |