E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Women with oestrogen receptor and/or progesterone receptor positive (ER/PR+ve) potentially hormone responsive recurrent or metastatic gynaecological cancer including selected patients with epithelial ovarian cancer, endometrial cancers, miscellaneous sarcomas and sex cord stromal tumours of the ovary |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
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 |
clinical benefit comprising either response or stable disease; Response as determined by Recist 1.1 in patients with measurable disease, CA125 in patients with ovarian cancer and no measurable disease and inhibin in patients with granulosa cell tumours with no measurable disease |
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E.2.2 | Secondary objectives of the trial |
* time to response in each sub-group
* response duration in each sub-group
* quality of life
* toxicity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
*patients with recurrent or metastatic gynaecological cancers. The specific subgroups are outlined below. All patients will have central review and analyses of ER/PR at a later date to confirm receptor status but entry to the study will be based on local hormone receptor analyses.
A.Epithelial ovarian cancer, primary peritoneal cancers and cancers of the fallopian tube.
*Asymptomatic patients with a rising CA125 after first line chemotherapy and GCIG defined CA125 progression (these patients should either have no measureable disease or small volume recurrence and the expectation they would not require chemotherapy within the next 12weeks)
*Borderline ovarian tumours, micro-invasive ovarian tumours and well differentiated low grade ovarian cancers. Apart from surgery, treatment options are very limited for these patients as these tumours are usually chemotherapy resistant but are also relatively indolent
*palinum resistant or refractory ovarian, fallopian tube and primary peritoneal cancer in patients in whom further chemotherapy is not indicated.
B.Endometrial cancer- patients that have measureable disease
C.Endometrial stromal sarcomas: patients that have measureable disease
D.Miscellaneous Sarcomas: includes leiomyosarcomas, adenosarcomas, carcinosarcomas and undifferentiated uterine sarcomas which have relapsed following standard treatment such as chemotherapy or patients in whom chemotherapy is not considered appropriate
E.Granulosa cell tumours and other sex cord stromal tumours: patients that have measurable disease and/or an elevated inhibin (total inhibin and/or inhibin B)level
*All patients must have ER and/or PR positive tumours by immunohistochemical evaluation based on the assessment at individual sites. Hormone receptor staining shoul be carried out on the original tumour. If not availbale, but the recurrent tumour is receptor positive, then these patients will also be eligible.
*post-menopausal as defined by: age 60 or more, or age 45-59 and satisfying the following criteria: amenorrhoea for at least 12 months and FSH in postmenopausal range with an intact uterus, or having had a bilateral oophorectomy
*evaluable disease defined as: measurable disease as per RECIST v1.1 OR CA125 as per GCIG criteria (for ovarian cancer subgroup) or elevated total inhibin and/or inhibin B (for granulosa cell sub-group)
*ECOG performance status 0-2
*Expected survival >3 months |
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E.4 | Principal exclusion criteria |
*prior therapy with an aromatase inhibitor
*patients receiving any hormone replacement therpay
*Inability to comply with study procedures
*Unable to give informed consent
*Other active malignancy or primary malignancy diagnosed within the previous 5 years, except for treated squamous or basal cell carcinoma of skin or cervical carcinoma
*significant hepatic (bilirubin >2x ULN) or renal dysfunction (creatinine > 3x ULN) |
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E.5 End points |
E.5.1 | Primary end point(s) |
* clinical benefit comprising either response or stable disease. Overall response rate as determined by RECIST v1.1 criteria (all tumour sub-groups) and/or CA125 tumour marker response by GCIG criteria (ovarian sub-group) or inhibin B/total inhibin (granulosa cell sub-group) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
*time to response in each sub-group
*response duration in each sub-group
*quality of life
*toxicity |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | No |
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 | No |
E.8.1.1 | Randomised | No |
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 | 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 | 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 | No |
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 |
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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
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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 | 3 |
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 | 3 |
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 |