Conventional Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial Oligometastases

NCT02759783 | Unknown Phase 2 DMC

• 3 other identifiers: CCR4323182152ISRCTN45961438
• Study Type: interventional
• Target: 245
• Locations: 2 countries
• Sites: 30

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.

Conditions

Prostate Cancer; Breast Cancer; Carcinoma, Non-Small-Cell Lung

Keywords

Radiotherapy; oligometastases; SBRT

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Time from randomisation to evidence of progression of cancer at any site or death from any cause

  60 months post treatment

Secondary Outcomes (6)

• Feasibility of recruitment

  3 years from first patient

• Feasibility of SBRT delivery

  3 years from first patient

• Overall Survival

  60 months post treatment

• Local lesion control

  60 months post treatment

• Clinical reported acute and late toxicity

  60 months post treatment

Other Outcomes (1)

• Freedom from widespread metastatic disease (FFWMD)

  Pre-treatment and at 3,6,9,12,15,18,21,24,30,36,42,48,54 and 60 months post treatment

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

Standard of care (SOC) is at the discretion of the local oncologist.

Other: Standard of Care

Standard of Care + SBRT

EXPERIMENTAL

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.

Radiation: SBRT; Other: Standard of Care

Interventions

SBRT RADIATION

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.

Also known as: Stereotactic body Radiotherapy, SABR

Standard of Care + SBRT

Standard of Care OTHER

Choice of standard of care treatment at the discretion of the local oncologist. This may include: Chemotherapy, Endocrine therapy, surgery, palliative radiotherapy

Standard of Care; Standard of Care + SBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• WHO performance status 0-2
• 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.
• Predicted life expectancy \> 6 months
• ≤ 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.
• 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)
• 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.
• 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.
• 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.
• Adequate baseline organ function to allow SBRT to all relevant targets dependent on location of metastatic subsite

You may not qualify if:

• Malignant pleural effusion
• Malignant peritoneal disease
• Any single metastasis \>6cm,( \>5cm for lung metastases)
• Prior radiotherapy to a site that precludes safe delivery of SBRT
• Co-morbidities precluding staging or follow up imaging, or precluding procedures required to facilitate SBRT
• 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
• 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)
• 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).
• 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.
• Prostate cancer patients receiving or have previously received abiraterone, enzalutamide or chemotherapy e.g. docetaxel.
• 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.
• Patients whose entry to the trial will cause unacceptable clinical delays to their planned management.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Institute of Cancer Research, United Kingdom: collaborator
• National Health Service, United Kingdom: collaborator

Study Sites (30)

Liverpool Hospital

Liverpool, New South Wales, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Location

GenesisCare - Adelaide Radiotherapy Centre

Adelaide, South Australia, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

Austin Health

Melbourne, Victoria, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Location

Churchill Hospital

Oxford, Oxfordshire, United Kingdom

Location

Mount Vernon Cancer Centre

London, Surrey, HA6 2RN, United Kingdom

Location

Belfast City Hospital

Belfast, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

The Beatson

Glasgow, United Kingdom

Location

Royal Surrey County Hospital

Guildford, United Kingdom

Location

St James's University Hospital

Leeds, United Kingdom

Location

Leicester Royal Infirmary

Leicester, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Guy's Hospital

London, United Kingdom

Location

St Bartholomew's Hospital

London, United Kingdom

Location

University College Hospital

London, United Kingdom

Location

The Christie Hospital

Manchester, United Kingdom

Location

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, United Kingdom

Location

James Cook University Hospital

Middlesbrough, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, United Kingdom

Location

Nottingham City Hospital

Nottingham, United Kingdom

Location

Weston Park Hospital

Sheffield, United Kingdom

Location

Royal Marsden Hospital

Sutton, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Radiosurgery; Standard of Care

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Vincent Khoo, MD

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2016
• First Posted: May 3, 2016
• Study Start: November 1, 2016
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: August 21, 2019

Record last verified: 2019-08

Locations

GB (21); AU (9)