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Trial registered on ANZCTR


Registration number
ACTRN12617000106336
Ethics application status
Approved
Date submitted
6/12/2016
Date registered
19/01/2017
Date last updated
13/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase II trial of durvalumab (Medi 4736) in advanced endometrial cancer
Scientific title
A Phase II trial of durvalumab (Medi 4736) in advanced endometrial cancer
A multi-centre Phase II trial to determine the activity and safety of durvalumab in advanced endometrial cancer
Secondary ID [1] 290191 0
ANZGOG 1601 (Australia New Zealand Gynaecological Oncology Group)
Universal Trial Number (UTN)
U1111-1186-8932
Trial acronym
PHAEDRA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced endometrial cancer 300338 0
Condition category
Condition code
Cancer 300200 300200 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants meeting the inclusion criteria of either MMR-proficient or MMR-deficient will be registered and administered 1500 mg durvalumab intravenously every 28 days until disease progression or prohibitive toxicity.
Intervention code [1] 295946 0
Treatment: Drugs
Comparator / control treatment
There is no control group and the two cohorts will not be compared
Control group
Uncontrolled

Outcomes
Primary outcome [1] 299686 0
To determine, in cohorts of DNA MMR-deficient and MMR-proficient endometrial cancer, Objective Tumour Response Rate according to iRECIST
Timepoint [1] 299686 0
Clinical assessments and bloods tests will occur every 4 weeks during treatment. CT chest, abdomen and pelvis at weeks 8, 16 and 24, then every 12 weeks until progression.
Secondary outcome [1] 327849 0
Objective Tumour Response Rate according to RECIST 1.1
Timepoint [1] 327849 0
Assessed via CT chest, abdomen and pelvis at weeks 8, 16 and 24, then every 12 weeks until disease progression.
Secondary outcome [2] 327850 0
Disease control rates
Timepoint [2] 327850 0
Assessed via CT chest, abdomen and pelvis scans at weeks 16 and 24 and defined by proportion of patients who have achieved Complete Response, Partial Response or Stable Disease
Secondary outcome [3] 327851 0
Progression free survival (PFS)
Timepoint [3] 327851 0
Clinical assessments and blood tests every 4 weeks during treatment. Ct chest, abdomen and pelvis at weeks 8, 16 and 24, then every 12 weeks until progression.
Secondary outcome [4] 327852 0
Overall survival (OS)
Timepoint [4] 327852 0
Clinical assessments every 4 weeks during treatment. 3 monthly after progression until death, or the date of last known alive follow-up .
Secondary outcome [5] 327853 0
Durations of Overall Tumour Response
Timepoint [5] 327853 0
Assessed via CT chest, abdomen and pelvis scans at weeks 8, 16 and 24, then every 12 weeks until progression.
Secondary outcome [6] 327854 0
Frequency and severity of Adverse Events (CTCAE v4.03)
Timepoint [6] 327854 0
Recorded from the first dose of study treatment until 90 days after cessation of durvalumab.
Secondary outcome [7] 327855 0
Aspects of health related quality of life (EORTC QLQ-C30)
Timepoint [7] 327855 0
Assessed at baseline and then every 4 weeks until progression.

Eligibility
Key inclusion criteria
Patients with advanced endometrial carcinoma suitable for chemotherapy
Adults, aged 18 years and older, with histologically or cytologically confirmed adenocarcinoma of endometrial origin
Advanced or recurrent disease that is not amenable to local therapy with curative intent such as surgical resection and/or radiotherapy
Assessment result for DNA mismatch repair (MMR) protein expression in tumour tissue by immunohistochemistry (IHC) must be available. This must include assessment for 4 MMR proteins: MLH1, MSH2, MSH6 and PMS2
Tumour tissue (FFPE) available for PD-L1 testing at a central laboratory
Agreement to undergo a repeat core biopsy of tumour tissue if the only available tumour tissue sample was obtained before previous chemotherapy or more than 1 year previously, and the investigator judges that the lesion can be biopsied without undue risk.
At least 1 target lesion according to RECIST v1.1
ECOG performance status of 0-2
Adequate bone marrow, renal and liver function
Willing and able to start treatment within 7 days of registration and to comply with all study requirements, including the timing and/or nature of the required treatment and assessments
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Suspected brain or leptomeningeal metastases, untreated brain metastases or current clinical or radiological progression of known brain metastases, or requirement for steroid therapy for brain metastases. Patients with treated brain metastases are eligible if they have been stable and off steroids for 3 weeks or longer.

Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks before registration, or persisting adverse events (>Grade 1) due to a previously administered agent.

Any condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone or equivalent dose of alternative corticosteroid) or other immunosuppressive medications within 28 days of durvalumab administration. Intranasal, inhaled or topical steroids are permitted in the absence of active autoimmune disease.

History of any known or suspected autoimmune disease other than vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to an autoimmune condition requiring only hormone replacement, or psoriasis not requiring systemic treatment within the last 2 years.

Prior allogeneic organ transplant, inflammatory bowel disease, pneumonitis, tuberculosis, or primary immunodeficiency.

Prior treatment with durvalumab, or with any other anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.

Life expectancy of less than 12 weeks.

Systemic infection requiring IV antibiotics within 14 days before the first dose of durvalumab.

Receipt of live attenuated vaccination within 30 days prior to enrolment.

Known history of interstitial lung disease from any cause

Mean QT interval corrected for heart rate (QTc) greater than or equal to 470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction

Myocardial infarction with 6 months prior to enrolment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, or active conduction system abnormalities.

History of another malignancy within 3 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 3 years after definitive primary treatment.

Significant infection, including chronic active hepatitis B, hepatitis C, or HIV.

Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.

Pregnancy, lactation, or inadequate contraception. Participants must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration.

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)
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
This is an open-label, uncontrolled, multi-centre, Phase II trial in two cohorts
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The total sample size for this study is 70 participants. In either of the cohorts, an objective tumour response rate of 5% or lower would be of little interest whereas an objective tumour response rate of 20% or more would be considered worthy of further research. Using a Simon's 2-stage minimax design with 90% power and 10% significance level requires 32 evaluable participants in each cohort. An additional 3 participants per cohort will be recruited to allow for ineligible participants and missing data.
The study will be analysed by intention to treat including all registered participants for efficacy analyses and all participants who received at least one dose of study treatment for safety analyses.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 7071 0
Cabrini Brighton - Brighton
Recruitment hospital [2] 7072 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 7073 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [4] 9543 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [5] 9544 0
Prince of Wales Hospital - Randwick
Recruitment hospital [6] 9545 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [7] 9546 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [8] 9547 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [9] 9548 0
Monash Medical Centre - Moorabbin campus - East Bentleigh
Recruitment hospital [10] 9549 0
Nambour General Hospital - Nambour
Recruitment hospital [11] 9550 0
Icon Cancer Care South Brisbane - South Brisbane
Recruitment hospital [12] 9551 0
Mater Adult Hospital - South Brisbane
Recruitment postcode(s) [1] 14798 0
3186 - Brighton
Recruitment postcode(s) [2] 14799 0
2050 - Camperdown
Recruitment postcode(s) [3] 14800 0
6009 - Nedlands
Recruitment postcode(s) [4] 18297 0
2065 - St Leonards
Recruitment postcode(s) [5] 18298 0
2031 - Randwick
Recruitment postcode(s) [6] 18299 0
2298 - Waratah
Recruitment postcode(s) [7] 18300 0
3000 - Melbourne
Recruitment postcode(s) [8] 18301 0
3084 - Heidelberg
Recruitment postcode(s) [9] 18302 0
3165 - East Bentleigh
Recruitment postcode(s) [10] 18303 0
4560 - Nambour
Recruitment postcode(s) [11] 18304 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 294563 0
Commercial sector/Industry
Name [1] 294563 0
AstraZeneca
Address [1] 294563 0
47 Talavera Road
Macquarie Park NSW 2113
Country [1] 294563 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
NHMRC Clinical Trials Centre
Level 6, Chris O'Brien Lifehouse
119-143 Missenden Road
CAMPERDOWN NSW 2050
Country
Australia
Secondary sponsor category [1] 293431 0
None
Name [1] 293431 0
Address [1] 293431 0
Country [1] 293431 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295998 0
SLHD (RPAH Zone)
Ethics committee address [1] 295998 0
RPAH Medical Centre
Suite 210A
100 Carillon Avenue
NEWTOWN NSW 2042
Ethics committee country [1] 295998 0
Australia
Date submitted for ethics approval [1] 295998 0
05/08/2016
Approval date [1] 295998 0
11/11/2016
Ethics approval number [1] 295998 0
X16-0346 &HREC/16/RPAH/472

Summary
Brief summary
The primary purpose of this trial is to evaluate the safety and efficacy of durvalumab for the treatment of advanced endometrial cancer.

Who is it for?
You may be eligible to enroll in this trial if you are aged 18 or over and have been diagnosed with advanced endometrial carcinoma which is suitable for chemotherapy.

Study details
All participants enrolled in this trial will receive an intravenous dose of durvalumab once every 28 days until the cancer is seen to have progressed, or until treatment side effects become intolerable. Participants will undergo continuous monitoring for side effects throughout treatment, as well as completing questionnaires and blood tests every four weeks, and CT scans every 8 to 12 weeks for the duration of treatment.

It is hoped that this trial will provide information on whether durvalumab is safe and effective for the treatment of advanced endometrial cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69166 0
Dr Yoland Antill
Address 69166 0
Cabrini Health
243 New Street
BRIGHTON VIC 3186
Country 69166 0
Australia
Phone 69166 0
+61 3 9508 8777
Fax 69166 0
Email 69166 0
yoland.antill@gmail.com
Contact person for public queries
Name 69167 0
Ms John Stark
Address 69167 0
NHMRC CTC
Locked Bag 77
CAMPERDOWN NSW 1450
Country 69167 0
Australia
Phone 69167 0
+61 2 9562 5000
Fax 69167 0
Email 69167 0
phaedra@ctc.usyd.edu.au
Contact person for scientific queries
Name 69168 0
Dr Yoland Antill
Address 69168 0
Cabrini Health
243 New Street
BRIGHTON VIC 3186
Country 69168 0
Australia
Phone 69168 0
+61 3 9508 8777
Fax 69168 0
Email 69168 0
yoland.antill@gmail.com

No data has been provided for results reporting
Summary results
Not applicable