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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02759783




Registration number
NCT02759783
Ethics application status
Date submitted
26/04/2016
Date registered
3/05/2016
Date last updated
21/08/2019

Titles & IDs
Public title
Conventional Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial Oligometastases
Scientific title
A Randomised Trial of Conventional Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial Oligometastases
Secondary ID [1] 0 0
182152
Secondary ID [2] 0 0
CCR4323
Universal Trial Number (UTN)
Trial acronym
CORE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Breast Cancer 0 0
Carcinoma, Non-Small-Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - SBRT
Other interventions - Standard of Care

Active comparator: Standard of Care - Standard of care (SOC) is at the discretion of the local oncologist.

Experimental: Standard of Care + SBRT - Patients randomised to SBRT will receive a dose and fractionation regimen dependent on the metastatic site and proximity to normal tissues. If allocated to SBRT, SBRT will precede SOC.


Treatment: Other: SBRT
Patients will receive a dose and fractionation regimen dependent on the metastatic site and proximity to normal tissues. If allocated to SBRT, SBRT will precede SOC. All patients should commence SOC therapy within 4 weeks of completing SBRT treatment.

Other interventions: Standard of Care
Choice of standard of care treatment at the discretion of the local oncologist. This may include: Chemotherapy, Endocrine therapy, surgery, palliative radiotherapy
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival
Timepoint [1] 0 0
60 months post treatment
Secondary outcome [1] 0 0
Feasibility of recruitment
Timepoint [1] 0 0
3 years from first patient
Secondary outcome [2] 0 0
Feasibility of SBRT delivery
Timepoint [2] 0 0
3 years from first patient
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
60 months post treatment
Secondary outcome [4] 0 0
Local lesion control
Timepoint [4] 0 0
60 months post treatment
Secondary outcome [5] 0 0
Clinical reported acute and late toxicity
Timepoint [5] 0 0
60 months post treatment
Secondary outcome [6] 0 0
Patient reported Quality of Life
Timepoint [6] 0 0
Pre-treatment and at 3,6,12,18 and 24 months post treatment

Eligibility
Key inclusion criteria
Inclusion criteria

1. Age = 18 years
2. WHO performance status 0-2
3. Histological confirmation of primary malignancy (histological confirmation of metastasis is not mandatory but should be performed in any situation where there is diagnostic uncertainty). Patients with breast, NSCLC or prostate primary malignancies are eligible.
4. Predicted life expectancy > 6 months
5. = 3 metastatic lesions (total). A maximum of 2 different organ systems (e.g. liver, lung, bone, nodal) may contain metastases but the total number of lesions must not exceed 3. For example, a patient with 3 liver metastases or 1 liver metastasis and 2 lung metastases would be eligible. A patient with 1 lung metastasis, 1 liver metastasis and an adrenal metastasis is ineligible.
6. All metastases must be visible, imaging defined targets and be suitable for treatment with SBRT in accordance with the dose fractionation options specified in the protocol. (See the associated CORE trial radiotherapy delivery guidelines for detailed SBRT guidance by metastatic site)
7. Patients who have received prior ablative therapy (e.g. surgery, RFA or SBRT) for metastatic disease are eligible, as long as this site is controlled on imaging at the point of trial entry and the total number of metastases over time since diagnosis of metastatic disease does not exceed 3. Patients with 2 or 3 metastases in which ablative therapy (e.g. surgery/RFA) to 1 site is deemed appropriate as part of standard therapy may be entered into the trial following successful delivery of the ablative treatment. Ablative therapy (e.g. surgery, RFA, cryoablation, SBRT) is not permissible as a standard of care option following randomisation for patients as part of the trial.
8. Only patients with metachronous metastatic disease presentation are eligible. Primary site must be controlled.

NSCLC patients with synchronous presentation of a single brain metastasis with the primary lung malignancy are eligible as long as both sites of disease have received radical treatment. Both primary lung site and solitary synchronous brain metastasis must be controlled at trial entry, and the total number of metastases over time including the brain metastasis must not exceed 3.

Permissible disease-free intervals are:

Breast: = 6 months from completion of radical treatment including any adjuvant therapy to diagnosis of metastases. Patients who have relapsed whilst on adjuvant endocrine therapy are eligible.

NSCLC: = 4 months from completion of radical treatment (not including any adjuvant chemotherapy) to diagnosis of metastases.

Prostate: = 6 months from completion of radical treatment including any adjuvant therapy to diagnosis of metastases. Patients who have relapsed whilst on adjuvant endocrine therapy are eligible.
9. Only patients who are systemic therapy naïve in the metastatic setting are eligible. Prior systemic therapy in the adjuvant setting is permitted. Patients who have had a change in endocrine therapy due to the diagnosis of oligometastatic disease can be entered into the CORE trial as long as entry is within 8 weeks of this change in therapy for prostate cancer patients and within 10 weeks of this change in therapy for breast cancer patients.
10. Adequate baseline organ function to allow SBRT to all relevant targets dependent on location of metastatic subsite
11. Negative pregnancy test (for women of childbearing potential)
12. Written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria

1. Intra-cranial metastases (not meeting above inclusion criterion 8).
2. Malignant pleural effusion
3. Malignant peritoneal disease
4. Any single metastasis >6cm,( >5cm for lung metastases)
5. Prior radiotherapy to a site that precludes safe delivery of SBRT
6. Co-morbidities precluding staging or follow up imaging, or precluding procedures required to facilitate SBRT
7. Loco-regional nodal relapse where surgery is considered the standard of care and is technically feasible. Patients with internal mammary chain or supraclavicular fossa lymph node relapses of breast cancer are eligible if SBRT dose constraints can be met. Patients with axillary nodal relapse from breast cancer are excluded
8. Spinal cord compression, or impingement of the cord or any other situation whereby the clinician feels that urgent radiotherapy to the spine is required (within 24 hours)
9. Any condition or significant clinical co-morbidities that preclude the safe delivery of SBRT (e.g. history of clinically significant diffuse interstitial lung disease if SBRT to lung metastases or lesions adjacent to lungs are considered or clinically significant colitis i.e. ulcerative colitis /Crohn's disease if SBRT to the pelvis or abdomen is considered).
10. Prostate cancer patients who have relapsed on Androgen Deprivation Therapy (ADT) which was started for biochemical relapse without staging investigations to define their relapse status, or who have relapsed on CAB which was started for biochemical relapse.
11. Prostate cancer patients receiving or have previously received abiraterone, enzalutamide or chemotherapy e.g. docetaxel.
12. Previous malignancy within the last 2 years (except basal cell carcinoma or squamous cell carcinoma of the skin), or if previous malignancy is expected to significantly compromise 5 year survival.
13. Patients whose entry to the trial will cause unacceptable clinical delays to their planned management.
14. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2024
Actual
Sample size
Target
Accrual to date
Final
245
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [5] 0 0
GenesisCare - Adelaide Radiotherapy Centre - Adelaide
Recruitment hospital [6] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 0 0
Austin Health - Melbourne
Recruitment hospital [8] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [9] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
- Liverpool
Recruitment postcode(s) [2] 0 0
- Waratah
Recruitment postcode(s) [3] 0 0
- Brisbane
Recruitment postcode(s) [4] 0 0
- Adelaide
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment postcode(s) [6] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
Oxfordshire
Country [2] 0 0
United Kingdom
State/province [2] 0 0
Surrey
Country [3] 0 0
United Kingdom
State/province [3] 0 0
Belfast
Country [4] 0 0
United Kingdom
State/province [4] 0 0
Birmingham
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Bristol
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Cambridge
Country [7] 0 0
United Kingdom
State/province [7] 0 0
Glasgow
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Guildford
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Leeds
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Leicester
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Manchester
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Middlesborough
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Newcastle upon Tyne
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Nottingham
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Sheffield
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Sutton
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Other
Name
Royal Marsden NHS Foundation Trust
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Institute of Cancer Research, United Kingdom
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
National Health Service, United Kingdom
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Metastatic spread of cancer from its primary site to distant organs is the commonest cause of death from cancer. The term oligometastases describes an intermediate metastatic state, in which cancer exists as a limited number of metastases at first, before cells acquire the ability to metastasise more widely. For the large majority of solid cancers, once metastatic disease has been diagnosed the chances of cure are small. There are several situations where this is not the case, but it is not known if stereotactic body radiotherapy (SBRT) for oligometastatic disease will alter outcomes or whether the toxicity burden of this treatment is justified. SBRT is targeted radiotherapy which destroys cancer cells in the area of the body it is aimed at however low dose radiation may be received by surrounding tissue.

It is difficult to quantify incidence of patients with multiple primary cancers developing at intervals that are representative of oligometastatic stage IV disease, (defined for the purposes of this trial as = 3 metastatic sites). However an increase in the use of surveillance imaging, together with improved diagnostic sensitivity has led to the diagnosis of patients with asymptomatic oligometastatic relapse becoming a more common clinical occurrence. The CORE study is a randomized controlled trial that will be conducted in patients with cancer in one of three primary sites where oligometastatic disease relapse is a common clinical scenario: breast, prostate and non-small cell lung cancer (NSCLC). The study will evaluate the use of SBRT in this patient population.

Eligible patients who consent to participate in this clinical trial will be randomized to receive standard care or standard care plus SBRT we hope to recruit approximately 206 patients to the study and the primary outcome measure is progression free survival.
Trial website
https://clinicaltrials.gov/study/NCT02759783
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Vincent Khoo, MD
Address 0 0
Royal Marsden NHS Foundation Trust
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02759783