Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000796088
Ethics application status
Approved
Date submitted
21/09/2010
Date registered
24/09/2010
Date last updated
27/10/2021
Date data sharing statement initially provided
10/05/2019
Date results provided
10/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase II study of aromatase inhibitors in women with potentially hormone responsive recurrent/metastatic gynaecological neoplasms
Scientific title
Phase II study of aromatase inhibitors in women with potentially hormone responsive recurrent/metastatic gynaecological neoplasms
Secondary ID [1] 252694 0
ANZGOG 0903 (Australia New Zealand Gynaecological Oncology Group)
Universal Trial Number (UTN)
Trial acronym
PARAGON
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hormone sensitive recurrent or metastatic gynecological cancers 258182 0
Condition category
Condition code
Cancer 258363 258363 0 0
Ovarian and primary peritoneal
Cancer 258364 258364 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Registered patients are prescribed a 1mg Anastrazole (Armidex) tablet daily (orally) until disease progression
Intervention code [1] 257202 0
Treatment: Drugs
Comparator / control treatment
There is no control group for this trial
Control group
Uncontrolled

Outcomes
Primary outcome [1] 259211 0
Overall response to treatment as determined by Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 criteria (all tumor sub-groups) or CA125 tumour marker response by Rustin criteria (ovarian sub-group) or inhibin (granulosa cell sub-group) as assessed at each visit by the Clinician
Timepoint [1] 259211 0
Assessed monthly for the first 3 months on trial then every 3 months until disease progression
Secondary outcome [1] 265600 0
Response to treatment in each tumor sub-group as determined by RECIST V1.1 criteria (all tumor sub-groups) or CA125 tumour marker response by Rustin criteria (ovarian sub-group) or inhibin (granulosa cell sub-group) as assessed at each visit by the Clinician
Timepoint [1] 265600 0
Assessed monthly for the first 3 months on trial then every 3 months until disease progression
Secondary outcome [2] 265601 0
Clinical benefit (complete response, partial response and stable disease) in those with measurable disease as determined by RECIST V1.1 criteria (all tumor sub-groups) or CA125 tumour marker response by Rustin criteria (ovarian sub-group) or inhibin (granulosa cell sub-group) as assessed at each visit by the Clinician
Timepoint [2] 265601 0
Assessed monthly for the first 3 months on trial then every 3 months until disease progression
Secondary outcome [3] 265602 0
Time to progression in patients without measureable disease as determined by RECIST V1.1 criteria (all tumor sub-groups) or CA125 tumour marker response by Rustin criteria (ovarian sub-group) or inhibin (granulosa cell sub-group) as assessed at each visit by the Clinician
Timepoint [3] 265602 0
Assessed monthly for the first 3 months on trial then every 3 months until disease progression
Secondary outcome [4] 265603 0
Time to response as determined by RECIST V1.1 criteria (all tumor sub-groups) or CA125 tumour marker response by Rustin criteria (ovarian sub-group) or inhibin (granulosa cell sub-group) as assessed at each visit by the Clinician
Timepoint [4] 265603 0
Assessed monthly for the first 3 months on trial then every 3 months until disease progression
Secondary outcome [5] 265604 0
Response duration as determined by RECIST V1.1 criteria (all tumor sub-groups) or CA125 tumour marker response by Rustin criteria (ovarian sub-group) or inhibin (granulosa cell sub-group) as assessed at each visit by the Clinician
Timepoint [5] 265604 0
Assessed monthly for the first 3 months on trial then every 3 months until disease progression
Secondary outcome [6] 265605 0
Quality of life as determined by Questionnaries
Timepoint [6] 265605 0
Quality of life will be assessed upon registration, monthly for the first 3 months on trial and then every 3 months until disease progression
Secondary outcome [7] 265606 0
Toxicity profile (including bone density) as detemined by a Bone mineral density scan (DXA) and blood tests
Timepoint [7] 265606 0
Toxicity profile will be assessed upon registration and then monthly for the first 3 months on trial
Secondary outcome [8] 265607 0
Maintain a register of these tumours and document the number of patients screened at participating sites and the percentage with Estrogen Receptor (ER)/Progesterone Receptor (PR) +ve tumours who are enrolled
Timepoint [8] 265607 0
Upon registration
Secondary outcome [9] 265608 0
Translational sub-study to correlate response rates with hormone receptor positivity as well as other biological markers that might predict for hormone response
Timepoint [9] 265608 0
After registration

Eligibility
Key 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 hormone receptor positivity according to local hormone receptor analyses.
A. Epithelial Ovarian Cancer, Primary Peritoneal Cancers and Cancers of the Fallopian Tube
(i) 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 12 weeks)
(ii) 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
(iii) Platinum 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 measurable disease
C. Endometrial Stromal Sarcomas: patients that have measurable disease
D. Miscellaneous Sarcomas: Includes leiomyosarcomas, adenosarcomas, carcinosarcomas and undifferentiated uterine sarcomas with measurable disease and relapse following standard treatment such as chemotherapy or patients in whom chemotherapy is not clinically indicated.
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 and in whom chemotherapy is not clinically indicated

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 hormone receptor positive, then these patients will also be eligible

Post-menopausal as defined by: (i) age 60 or more, or (ii) age 45–59 and satisfying the following criteria: Amenorrhoea for at least 12 months and FSH in postmenopausal range with an intact uterus, or (iii) age equal to 18 or more and 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 Performance status 0-2

Expected survival > 3months
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Prior therapy with an aromatase inhibitor, tamoxifen or progestagens

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 in situ cervical carcinoma

Significant hepatic (bilirubin >2x ULN) or renal dysfunction (creatinine >3x ULN)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients can be registered for the trial by faxing an enrolment form to the National Health and Medical Reseach Council (NHMRC) Clinical Trials Centre. There is no control group so all patients are treated with the same type and amount of study drug
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/08/2011
Actual
11/01/2012
Date of last participant enrolment
Anticipated
Actual
28/06/2016
Date of last data collection
Anticipated
30/06/2020
Actual
30/04/2020
Sample size
Target
350
Accrual to date
Final
333
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
Recruitment outside Australia
Country [1] 2910 0
United Kingdom
State/province [1] 2910 0
Newcastle
Country [2] 2911 0
New Zealand
State/province [2] 2911 0
Country [3] 8012 0
Belgium
State/province [3] 8012 0
UZ Leuven

Funding & Sponsors
Funding source category [1] 257660 0
Government body
Name [1] 257660 0
Cancer Australia
Country [1] 257660 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
NHMRC Clinical Trials Centre
The University of Sydney
Locked Bag 77
Camperdown NSW 1450
Country
Australia
Secondary sponsor category [1] 256900 0
None
Name [1] 256900 0
Address [1] 256900 0
Country [1] 256900 0
Other collaborator category [1] 251521 0
Charities/Societies/Foundations
Name [1] 251521 0
Australia New Zealand Gynaecological Oncology Group (ANZGOG
Address [1] 251521 0
Australia New Zealand Gynaecological Oncology Group
Level 6, Chris O'Brien Lifehouse
119-143 Missenden Road
CAMPERDOWN NSW 2050
Country [1] 251521 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259672 0
Sydney Local Health District (RPAH Zone) Ethics Review Committee
Ethics committee address [1] 259672 0
Ethics committee country [1] 259672 0
Australia
Date submitted for ethics approval [1] 259672 0
08/11/2010
Approval date [1] 259672 0
12/07/2013
Ethics approval number [1] 259672 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31646 0
Prof Michael Friedlander
Address 31646 0
Prince of Wales Hospital
Medical Oncology Clinical Trials Unit
Level 2, High St,
Randwick, NSW, 2031
Country 31646 0
Australia
Phone 31646 0
+61 2 9282 2606
Fax 31646 0
Email 31646 0
[email protected]
Contact person for public queries
Name 14893 0
PARAGON Trial Coordinator
Address 14893 0
NHMRC CTC
Locked Bag 77
Camperdown NSW 1450
Country 14893 0
Australia
Phone 14893 0
+61 2 9562 5000
Fax 14893 0
+61 2 9562 5094
Email 14893 0
[email protected]
Contact person for scientific queries
Name 5821 0
Professor Michael Friedlander
Address 5821 0
Prince of Wales Hospital High Street, Randwick NSW 2031
Country 5821 0
Australia
Phone 5821 0
+61 2 9282 2606
Fax 5821 0
+61 2 9382 2588
Email 5821 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseParagon (ANZGOG-0903): Phase 2 study of anastrozole in women with estrogen or progesterone receptorypositive platinum-resistant or -refractory recurrent ovarian cancer.2017https://dx.doi.org/10.1097/IGC.0000000000000978
EmbasePARAGON (ANZGOG-0903): A phase 2 study of anastrozole in asymptomatic patients with estrogen and progesterone receptor-positive recurrent ovarian cancer and CA125 progression.2019https://dx.doi.org/10.3802/jgo.2019.30.e86
EmbasePhase 2 study of anastrozole in recurrent estrogen (ER)/progesterone (PR) positive endometrial cancer: The PARAGON trial - ANZGOG 0903.2019https://dx.doi.org/10.1016/j.ygyno.2019.05.007
EmbaseA phase 2 study of anastrozole in patients with oestrogen receptor and/progesterone receptor positive recurrent/metastatic granulosa cell tumours/sex-cord stromal tumours of the ovary: The PARAGON/ANZGOG 0903 trial.2021https://dx.doi.org/10.1016/j.ygyno.2021.07.024
EmbasePhase 2 study of anastrozole in patients with estrogen receptor/progesterone receptor positive recurrent low-grade endometrial stromal sarcomas: The PARAGON trial (ANZGOG 0903).2021https://dx.doi.org/10.1016/j.ygyno.2021.02.016
EmbasePhase 2 study of anastrozole in rare cohorts of patients with estrogen receptor/progesterone receptor positive leiomyosarcomas and carcinosarcomas of the uterine corpus: The PARAGON trial (ANZGOG 0903).2021https://dx.doi.org/10.1016/j.ygyno.2021.09.010
EmbaseUpdate on new treatments for rare ovarian tumours.2023https://dx.doi.org/10.1097/GCO.0000000000000836
N.B. These documents automatically identified may not have been verified by the study sponsor.