PARAGON - Phase II study of aromatase inhibitors in women with potentially hormone responsive recurrent/metastatic gynaecological neoplasms

Phase 1

• Conditions: Patients with potentially hormone responsive recurrent or metastatic gynaecological cancers from following subgroups:A - Epithelial ovarian cancer, primary peritoneal cancers and cancers of the fallopian tubeB- Endometrial cancerC- Endometrial Stromal SarcomasD- Miscellaneous SarcomasE- Granulosa Cell Tumours and other Sex Tumours * UK sites will only enter patients to subgroups B-E *; MedDRA version: 14.1Level: LLTClassification code 10026310Term: Malignant neoplasm of ovarySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10014760Term: Endometrial neoplasm malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-000501-52-GB
• Lead Sponsor: Greater Glasgow and Clyde

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-08-23
• Last Update Posted: 13 October 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 350

Inclusion Criteria

- Patient with recurrent or metastatic gynaecological cancer. 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
B- Endometrial Cancer:Patients that have measurable disease
C- Endometrial Stromal Sarcomas: Patients that have measurable disease
D - 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.
E -Granulosa Cell Tumours and other Sex Cord Tumours : patients that measurable disease and/or elevated inhibin (total inhibin and/or inhibin B? level
** Please note UK centres will only enter patients to subgroups B-E of the study.
- 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.
- Post menopausal as defined by: i.) aged 60 or more, or ii.) age 45-59 and satisfting 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; i.)measurable disease as per RECIST v1.1, OR
ii.) CA125 as per GCIG criteria (for ovarian cancer subgroup) OR iii.)elevated total inhibin and/or inhibin B (for granulosa cell sub-group)
- ECOG peformance status 0-2
- Expected survival > 3 months
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

- Prior therapy with an aromatase inhibitor
- Patients receiving any hormone replacement therapy
- 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 >2xULN) or renal dysfunction (creatinine>3x ULN)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The principal objective of the study is clinical benefit rate determined by the proportion of patients experiencing either stable disease or response within 3 months of commencing treatment.;Secondary Objective: The secondary objectives of the study are:<br>- Time to response for each subgroup<br>- Response duration in each subgroup<br>- Quality of Life<br>- Toxicity;Primary end point(s): The primary endpoint of the study is evidence of response within 3 months of commencing treatment. This will be determined radiologically by RECIST v1.1 or CA125 or inhibin (depending on the specific tumour type).;Timepoint(s) of evaluation of this end point: This will be determined radiologically by RECIST v1.1 or CA125 or inhibin (depending on the specific tumour type).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Progression free survival in each subgroup<br>- Response duration in each subgroup<br>- Average scores for aspects of QOL during treatment<br>- Proportion of patients experiencing grade 3 or 4 toxicities;Timepoint(s) of evaluation of this end point: The endpoints will be assessed at each clinic visit. Patients will be assessed monthly for first 3 months on trial then every 3 months disease progression.