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Trial registered on ANZCTR


Registration number
ACTRN12620001212943
Ethics application status
Approved
Date submitted
29/07/2020
Date registered
16/11/2020
Date last updated
16/11/2020
Date data sharing statement initially provided
16/11/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Stereotactic Radiotherapy for Oligoprogressive ER-positive Breast Cancer. AVATAR.
Scientific title
Effect of Stereotactic Radiotherapy , on time to change in systemic therapy among women with Oligoprogressive ER-positive Breast Cancer (ER-positive, HER2-negative advanced breast cancer)
Secondary ID [1] 301920 0
Nil known
Universal Trial Number (UTN)
Trial acronym
AVATAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 318431 0
ER-positive, HER2-negative advanced breast cancer 318432 0
Advanced breast cancer 318433 0
Condition category
Condition code
Cancer 316439 316439 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients who are receiving an Aromatase Inhibitor in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor for at least 6 months, will be offered Stereotactic Radiotherapy for up to 5 oligoprogressive lesions.
Stereotactic Radiotherapy will be given preferably as 1 dose of 20Gy, if this isn't suitable then it can be given over 3 days at 10Gy per day or over 5 days at 7Gy per day.
The radiotherapy will be given during the week off CDK4/6 inhibitor and the patient must stop this at least 3 days before radiotherapy and not begin again until 3 days after it ends.
Intervention code [1] 318199 0
Treatment: Drugs
Intervention code [2] 318200 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324589 0
The primary outcome of this study is to measure time to change or cessation of systemic therapy (AI + CDK 4/6 inhibitor), defined as the time from commencement of stereotactic radiotherapy to change in systemic therapy.. This outcome will be assessed by treating physician at patient visit .
Timepoint [1] 324589 0
Assessed every 3 months for two years after the completion of treatment.

Secondary outcome [1] 385121 0
Measure Progression free survival which will be assessed each three months from date of commencement of SRT to date of first evidence of progression or death by any cause. This will be assessed by data linkage to medical records.
Timepoint [1] 385121 0
Assessed every three months for two years following completion of treatment
Secondary outcome [2] 387319 0
overall survival and treatment related toxicity
Timepoint [2] 387319 0
overall survival and treatment toxicity assessed every three months from date of commencement of SRT to date of death by any cause, assessed by data-linkage to medical records.
Secondary outcome [3] 387320 0
Safety will be assessed using CTCAE v5.0 and the maximum toxicity grade, per patient of each adverse event will be derived'.
Timepoint [3] 387320 0
Assessed every three months for two years following completion of treatment.

Eligibility
Key inclusion criteria
1. Male or female, 18 years of age or older
2. Patients with histologically proven ER-positive, HER2-negative advanced breast cancer receiving an AI in combination with a CDK 4/6 inhibitor. Biopsy of metastatic disease if technically feasible but not mandatory.
3. Patients must have evidence of extracranial metastatic disease with or without intracranial metastases.
4. Radiological evidence of stable or responding disease to an AI in combination with a CDK 4/6 inhibitor for a period of at least 6 months prior to study entry. (Patient must have ongoing stability/response in at least one lesion at the time of registration).
5. Evidence of new or existing OPD in 1-5 lesions. With reference to RECIST 1.132 and or PERCIST 1.033, OPD is defined as follow:
a. Using CT for intracranial or extracranial OPD:
i. greater than 5 mm increase in the diameter of an existing lesion OR
ii. more than 20% increase in the diameter of an existing lesion on 2 consecutive imaging studies at least 2 months apart OR
iii. The appearance of one or more new soft tissue lesions, measuring more than 5 mm.
b. Using Positron Emission Tomography for extracranial OPD:
i. greater than 30% increase in 18F-FDG SUV peak, with more than 0.8 SUV units increase in tumour SUV from the baseline scan in pattern typical of tumour and not of infection/treatment effect OR
ii. New 18F-FDG avid lesions typical of cancer (including new bone lesion) and not related to treatment effect and/or infection.
6. For patients with liver or lung metastases, maximum of 3 oligoprogressive lesions in single organ.
7. All OPD must be amenable to SRT.
a. Patients with risk of bone fracture are not candidate for SRT
8. For patients with intracranial metastases, SRT is the preferred treatment option, however, if clinical assessment indicated that upfront surgery is better, then post-operative SRT to the surgical cavity is recommended.
9. ECOG performance status 0-2.
10. Life expectancy of greater than 6 months.
11. Provision of written informed consent.
12. Clinician and participant are willing to continue current line of therapy.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnancy or lactation at the time of study entry.
2. Evidence of more than one clone of metastatic disease e.g. ER-positive and ER-negative and or HER2-positive disease. (To exclude those with some ER-positive and some TNBC or HER2-positive disease).
3. Evidence of Leptomeningeal disease.
4. Evidence of Malignant cord compression.
5. Previous chemotherapy for metastatic disease (chemo for primary breast cancer is allowed).
6. Contraindication to radiotherapy.
7. Previous radiotherapy in which the treated area planned to receive treatment is greater or equal to EQD2 40 Gy.
8. Any condition deeming the patient unsuitable to comply with the study.


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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Descriptive statistics of baseline characteristics of all treated patients will be reported. Continuous variables will be described as mean, standard deviation, median, interquartile range, minimum and maximum, and qualitative variables will be described as counts and percentages. Unless stated otherwise, the calculation of proportions will not include the missing category in the denominator. No imputation for missing value is intended and all confidence intervals provided will be 95% two-sided, unless stated otherwise.
Time to change in systemic therapy, PFS and OS curves will be described using Kaplan-Meier methods. The curves will be presented with 95% confidence intervals. Estimates at key time points (e.g. 6 and 12 months) and median times will also be provided with respective 95% confidence interval. An event history plot will also be provided. A cut-off date for follow-up will be determined at the time of analysis. The cut-off date will be chosen to enable data on follow-up to that date to be collected, where possible, on all living patients. All events occurring after this date will be ignored in the analysis in order to minimise reporting bias.
Safety will be assessed using CTCAE v5.0 and the maximum toxicity grade per patient of each adverse event will be derived and presented in table format. The number of patients who suffer from grade 3 or higher toxicities (for each toxicity type and overall) will be provided.

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)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 17172 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 17173 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 17174 0
Genesis Cancer Care - Wesley - Auchenflower
Recruitment hospital [4] 17175 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [5] 17176 0
The Townsville Hospital - Douglas
Recruitment hospital [6] 17994 0
The Canberra Hospital - Garran
Recruitment hospital [7] 17995 0
Peter Maccallum Cancer Centre - Moorabbin Campus - Bentleigh East
Recruitment postcode(s) [1] 31953 0
2605 - Garran
Recruitment postcode(s) [2] 30872 0
3000 - Melbourne
Recruitment postcode(s) [3] 30874 0
3065 - Fitzroy
Recruitment postcode(s) [4] 31954 0
3165 - Bentleigh East
Recruitment postcode(s) [5] 30871 0
3168 - Clayton
Recruitment postcode(s) [6] 30873 0
4066 - Auchenflower
Recruitment postcode(s) [7] 30875 0
4814 - Douglas

Funding & Sponsors
Funding source category [1] 306333 0
Hospital
Name [1] 306333 0
Peter Mac Callum Cancer Centre
Address [1] 306333 0
305 Grattan Street
Melbourne Victoria
3000
Country [1] 306333 0
Australia
Primary sponsor type
Hospital
Name
Peter Mac Callum Cancer Centre
Address
305 Grattan Street
Melbourne Victoria
3000
Country
Australia
Secondary sponsor category [1] 306831 0
None
Name [1] 306831 0
Address [1] 306831 0
Country [1] 306831 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306544 0
Peter MacCallum Cancer Centre Human Research Ethics Committee
Ethics committee address [1] 306544 0
305 Grattan Street
Melbourne 3000
Victoria
Ethics committee country [1] 306544 0
Australia
Date submitted for ethics approval [1] 306544 0
09/04/2020
Approval date [1] 306544 0
15/07/2020
Ethics approval number [1] 306544 0
HREC/62313/PMCC.Peter Mac No 20/54

Summary
Brief summary
Who is it for?
This study will investigate the safety and efficacy of Stereotactic Radiotherapy treatment in combination with aromatase inhibitor and cyclin-dependent kinase (CDK) 4/6 inhibitor for metastatic breast cancer." You may be eligible to join this study if you are aged 18 and above, have histologically proven ER-positive, HER2-negative advanced breast cancer with metastases and receiving an aromatase inhibitor in combination with a CDK 4/6 inhibitor

Study details
All participants in this study receive stereotactic radiotherapy (between 1 -5 doses as ascertained by treating Doctor after consultation) in combination with prescribed aromatase inhibitor and CDK 4/6 inhibitor.

Participants will be monitored for reactions and treatment effectiveness, and provide blood and urine for analysis throughout the 2 year study.

This research will give us information about whether adding radiotherapy to a CDK 4/6 inhibitor increases the amount of time participants can stay on CDK 4/6 inhibitor therapy.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104234 0
Dr Dr Steven David MBBS; FRANZCR Radiation Oncologist
Address 104234 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne 3000 Victoria
Country 104234 0
Australia
Phone 104234 0
+61 3 9928 8924
Fax 104234 0
+61 3 9928 8918
Email 104234 0
Steven.David@petermac.org
Contact person for public queries
Name 104235 0
Ms Suzie Roache
Address 104235 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne 3000 Victoria
Country 104235 0
Australia
Phone 104235 0
+61 3 8559 8481
Fax 104235 0
Email 104235 0
Suzie.Roache@petermac.org
Contact person for scientific queries
Name 104236 0
Ms Suzie Roache
Address 104236 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne 3000 Victoria
Country 104236 0
Australia
Phone 104236 0
+61 3 8559 8481
Fax 104236 0
Email 104236 0
Suzie.Roache@petermac.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All patient's data will be stored in a confidential database with controlled access provided to only those involved in the project. At the end of the study only aggregated reports of study outcomes will be published.
What supporting documents are/will be available?
No other documents available
Summary results
No Results