Condition category
Cancer
Date applied
19/09/2016
Date assigned
02/11/2016
Last edited
31/10/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Dr Mary Yip Braidley

ORCID ID

Contact details

The Institute of Cancer Research
15 Cotswold Road
Belmont
Sutton
SM2 5NG
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

31452

Study information

Scientific title

CORE: A randomized trial of conventional care versus radioablation (stereotactic body radiotherapy) for extracranial oligometastases

Acronym

CORE

Study hypothesis

The principal aim of the trial is to assess whether the addition of SBRT to standard therapy improves survival outcomes, focusing on common primary tumour sites where oligometastatic disease is encountered.

Ethics approval

London-Central Research Ethics Committee, 09/05/2016, ref: 16/LO/0529

Study design

Randomised; Interventional; Design type: Treatment, Surgery

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Breast; UKCRC code/ Disease: Cancer/ Malignant neoplasms of ill-defined, secondary and unspecified sites

Intervention

Patients will be randomised between SOC and SBRT + SOC in a 1:1 ratio. Patients will be randomised at different stages of their disease depending on the primary tumour site and in accordance with the inclusion and exclusion criteria. Treatment allocation will use minimisation with balancing factors of primary tumour site (breast, NSCLC, prostate) and centre. In tumour sites where there is felt to be a further important prognostic variable which may affect the primary PFS endpoint, a further stratification will be performed, as outlined below, to ensure the 2 treatment groups are balanced.
Breast – ER+ vs ER-
NSCLC – EGFR+ vs EGFR-
Prostate – endocrine naïve vs castrate resistant

SOC only arm: In the SOC only arm, the choice of SOC treatment is at the discretion of the local oncologist (chemotherapy, biological therapy, endrocrine therapy, surgery, palliative radiotherapy or observation).

SBRT + SCO arm: Patients randomised to SBRT+SOC will receive a dose and fractionation regimen dependent on the metastatic site and proximity to dose limiting organs and normal tissues. The average scheme would be 3 treatments over 5 days but the maximum period of SBRT duration could be 8 treatments over 19 days. After SBRT treatment, the patient will be treated with the SOC treatment at the discretion of the local oncologist.

All patients will be reviewed every 3 months with a clinical examination and tumour markers (where applicable) during years 1 and 2, and 6 monthly thereafter to 5 years. Staging and follow up imaging protocols will be tumour type dependent:

1. Breast: 3 monthly CT scans for years 1 and 2, and 6 monthly thereafter to 5 years.
2. NSCLC: 3 monthly CT scans for years 1 and 2, 6 monthly to year 3, then annually to 5 years.
3. Prostate: CT scans will be performed at 6, 12 and 24 months with imaging triggered by appropriate PSA rises.

All patients will have a toxicity assessment at each clinic visit and patient reported quality of life (QOL) assessment at 3, 6, 12, 18 and 24 months.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Progression free survival is measured using RECIST at baseline, 3, 6, 9, 12, 15, 18, 21,24, 30, 36, 42, 48, 54 and 60 months post randomisation.

Secondary outcome measures

1. Recruitment rate is defined by the proportion of patients recruited into the trial versus the number of patients required
2. SBRT deliverability is defined by the proportion of patients allocation SBRT who received SBRT and within dosimetric constraints outlined in the protocol versus the number of patients allocated SBRT
3. Overall survival is defined as time from randomisation until the time of death from any cause
4. Local lesion control is assessed using RECIST at baseline, 3, 6, 9, 12, 15, 18, 21,24, 30, 36, 42, 48, 54 and 60 months post randomisation.
5. Clinician reported acute and late radiation related toxicity is measured using CTCAE version 4 and RTOG at baseline, end of treatment, 3, 6, 9, 12, 15, 18, 21,24, 30, 36, 42, 48, 54 and 60 months post randomisation
6. Patient reported quality of life is measured using the EORTC QLQ C30 and EQ-5D questionnaires at baseline, end of treatment, 3, 6, 9, 12, 18 and 24 months post randomisation

Overall trial start date

27/01/2015

Overall trial end date

01/10/2019

Reason abandoned

Eligibility

Participant 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 after ablative treatment, following successful delivery of clinical treatment.
8. Metachronous metastatic disease presentation only. Primary site must be controlled. Disease-free interval from completion of radical treatment (including any adjuvant therapy) to diagnosis of metastases:
8.1. Breast: ≥ 6 months. Patients who have relapsed whilst on adjuvant endocrine therapy are eligible.
8.2. NSCLC: ≥ 4 months
8.3. Prostate: ≥ 6 months. Patients who have relapsed whilst on adjuvant endocrine therapy are eligible
9. Systemic therapy naïve in the metastatic setting
10. Adequate baseline organ function to allow SBRT to all relevant targets dependent on location of metastatic subsite for necessary baseline investigations)
11. Negative pregnancy test (for women of childbearing potential)
12. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
13. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 206; UK Sample Size: 206

Participant exclusion criteria

1. Intra-cranial metastases
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 or regional field radiotherapy is standard of care. Patients with supraclavicular, axillary and internalmammary nodal relapse from breast cancer are excluded
8. Spinal cord compression
9. Any condition or significant clinical co-morbidities that precludes the safe delivery of SBRT (eg history of clinically significant diffuse interstitial lung disease if SBRT to lung metastases or lesions adjacent to lungs are considered or clinically significant colitis ie ulcerative colitis /Crohn’s disease if SBRT to the pelvis or abdomen is considered)
10. Prostate cancer patients previously relapsing on Androgen Deprivation Therapy (ADT) or CAB and receiving abiraterone, enzalutamide or docetaxel are ineligible
11. Patients whose entry to the trial will cause unacceptable clinical delays to their planned management

Recruitment start date

07/10/2016

Recruitment end date

07/10/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

The Institute of Cancer Research
Clinical Trials and Statistics Unit (ICR-CTSU) 15 Cotswold Road Belmont
Sutton
SM2 5NG
United Kingdom

Sponsor information

Organisation

Royal Marsden NHS Foundation Trust

Sponsor details

Research & Development Office
Downs Road
Sutton
SM2 5PT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The main trial results will be published in a peer-reviewed journal, on behalf of all collaborators. Study results will be published 1 year after trial ends.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are/will be available upon request from core-icrctsu@icr.ac.uk

Intention to publish date

01/10/2020

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

31/10/2017: Internal review. 24/11/2016: Cancer Help UK lay summary link added.