Plain English Summary
Phase II study of Aromatase inhibitors in women with potentially hormone Responsive recurrent/metastatic Gynaecological Neoplasms (PARaGoN)
Determine clinical benefit rate by the proportion of patients experiencing either stable disease or response within 3 months of commencing treatment.
NRES Committee North East - Newcastle & North Tyneside, 07 December 2011 ref: 11/NE/0214
Single arm prospective phase II study
Primary study design
Secondary study design
Non randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Hormone responsive recurrent/metastatic gynaecological neoplasms
Patients will be eligible for the trial if they have hormone responsive recurrent /metastatic gynaecological cancer which is unlikely to be cured by standard treatment. To be considered for the trial the original tumour specimens will be re examined to ensure that they express the oestrogen receptor.
Patient will give written informed consent before enrollment, following enrollment all patients will be given a standard dose of the oral aromatase inhibitor anastrazole of 1mg per day. Patients will stay on treatment until progression or until 5 years after enrollment, whichever is the sooner.
Primary outcome measures
Clinical benefit rate determined by the proportion of patients experiencing either stable disease or response within 3 months of commencing treatment. This will be determined radiologically by RECIST v1.1 or CA125 of inhibin (depending on the specific tumour type).
Secondary outcome measures
Progression free survival: this will be determined radiologically by Response Evaluation Criteria in Solid tumours (RECIST v1.1) or CA125 tumour marker response or inhibin.
1. Response duration in each subgroup: this will be determined radiologically by RECIST v1.1 or CA125 or inhibin.
2. Quality of life (QOL): will be assessed in the study using EORTC QLQ-C30 core questionnaire and the Functional Assessment of Cancer Therapy Endocrine Symptoms subscale.
3.Toxicity :Proportion of patients experiencing grade 3 or 4 toxicities, adverse events will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Patient with recurrent or metastatic gynaecological cancer. The specific subgroups are outlined below. All patients will have central review and analyses of oestrogen receptor/progesterone receptor (ER/PR) at a later date to confirm receptor status but entry to the study will be based on local hormone receptor analyses.
1.1. Epithelial ovarian cancer, primary peritoneal cancers and cancers of the fallopian fube
1.2. Endometrial cancer: patients that have measurable disease
1.3. Endometrial stromal sarcomas: patients that have measurable disease
1.4. Miscellaneous sarcomas: includes leimyosarcomas, adenosarcomas, carcinoasrcomas and undifferentiated sarcomas which have relapsed following standard treatment such as chemotherapy or patients in whom chemotherapy is not considered appropriate.
1.5. Granulosa cell tumours and other sex cord tumours: patients with measurable disease and/or elevated inhibin (total inhibin and/or inhibin B? level
1.6. UK centres will only enter patients to subgroups B-E of the study
2. All patients must have ER and/or PR positive tumours by immunohistochemical evaluation based on the assessment at individual sites. Hormone receptor staining should be carried out on the original tumour. If not available, but the recurrent tumour is receptor positive, then these patients will be eligible.
3. Post menopausal as defined by:
3.1. Aged 60 or more, or
3.2. Age 45-59 and has amenorrhoea for at least 12 months and follicle-stimulating hormone (FSH) in postmenopausal range with an intact uterus, or having had a bilateral oophorectomy
4. Evaluable disease defined as
4.1. Measurable disease as per Response Evaluation Criteria In Solid Tumours (RECIST) v1.1, or
4.2. Cancer antigen 125 (CA125) as per GCIG criteria (for ovarian cancer subgroup) or
4.3. Elevated total inhibin and/or inhibin B (for granulosa cell sub-group)
5. Eastern Cooperative Oncology Group (ECOG) peformance status 0-2
6. Expected survival > 3 months
Target number of participants
Participant exclusion criteria
Prior therapy with an aromatase inhibitor:
1. Patients receiving any hormone replacement therapy
2. Inability to comply with study procedures
3. Unable to give informed consent
4. 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
5. Significant hepatic (bilirubin >2xULN) or renal dysfunction (creatinine>3x ULN)
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Northern Institute for Cancer Research
Newcastle upon Tyne
NHS Greater Glasgow and Clyde (UK)
Research and Development
The Tennent Institute
38 Church Street
Cancer Research UK (UK) ref: A12846
Funding Body Type
private sector organisation
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting