Conventional Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial Oligometastases (CORE)
A Randomised Trial of Conventional Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial Oligometastases
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.
연구 개요
상세 설명
CORE is a phase II/III, multi-centre, non-blinded, parallel group randomised controlled trial in patients with breast, prostate or NSCLC primary cancer comparing standard of care (SOC) with or without SBRT for extra-cranial metastases. The aim of the phase II study is to demonstrate 1) feasibility of recruitment, 2) deliverability of the study in a multi-centre setting and 3) activity of SBRT, based on progression free survival, across the three tumour types. If all three aims are achieved the trial will be amended to roll into parallel tumour-site specific phase III trials.
Eligible patients are those with either primary breast, prostate or NSCLC who have presented with ≤3 extra-cranial, metachronous, oligometastases, all suitable for SBRT. Patients will be randomised in a 1:1 ratio to either SOC or SOC with the addition of SBRT. Choice of SOC treatment is at the discretion of the local oncologist and defined per patient prior to randomisation (see section 8). 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. Treatment will take place within 6 weeks of randomisation. The average scheme would be 3 treatments over 5 days but the maximum period of SBRT duration could be 8 treatments over 19 days.
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:
- Breast: 3 monthly CT scans for years 1 and 2, and 6 monthly thereafter to 5 years.
- NSCLC: 3 monthly CT scans for years 1 and 2, 6 monthly to year 3, then annually to 5 years.
- Prostate: CT scans will be performed at 6, 12 and 24 months with imaging triggered by appropriate PSA rises. A rising PSA defined as 2 successive PSA rises from nadir, measured a minimum of 4 weeks apart. If the overall PSA rise has a doubling time of ≥ 3 months or the PSA level has doubled the original PSA value at trial entry or if clinically indicated, then restaging should be considered.
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.
연구 유형
등록 (실제)
단계
- 2 단계
- 3단계
연락처 및 위치
연구 장소
-
-
-
Belfast, 영국
- Belfast City Hospital
-
Birmingham, 영국
- Queen Elizabeth Hospital
-
Bristol, 영국
- Bristol Haematology and Oncology Centre
-
Cambridge, 영국
- Addenbrooke's Hospital
-
Glasgow, 영국
- The Beatson
-
Guildford, 영국
- Royal Surrey County Hospital
-
Leeds, 영국
- St James's University Hospital
-
Leicester, 영국
- Leicester Royal Infirmary
-
London, 영국, SW3 6JJ
- Royal Marsden Hospital
-
London, 영국
- University College Hospital
-
London, 영국
- St Bartholomew's Hospital
-
London, 영국
- Guy's Hospital
-
Manchester, 영국
- The Christie Hospital
-
Middlesborough, 영국
- James Cook University Hospital
-
Newcastle upon Tyne, 영국
- Freeman Hospital
-
Nottingham, 영국
- Nottingham City Hospital
-
Sheffield, 영국
- Weston Park Hospital
-
Sutton, 영국
- Royal Marsden Hospital
-
Wirral, 영국
- Clatterbridge Cancer Centre
-
-
Oxfordshire
-
Oxford, Oxfordshire, 영국
- Churchill Hospital
-
-
Surrey
-
London, Surrey, 영국, HA6 2RN
- Mount Vernon Cancer Centre
-
-
-
-
New South Wales
-
Liverpool, New South Wales, 호주
- Liverpool Hospital
-
Waratah, New South Wales, 호주
- Calvary Mater Newcastle
-
-
Queensland
-
Brisbane, Queensland, 호주
- Royal Brisbane and Women's Hospital
-
Brisbane, Queensland, 호주
- Princess Alexandra Hospital
-
-
South Australia
-
Adelaide, South Australia, 호주
- Royal Adelaide Hospital
-
Adelaide, South Australia, 호주
- GenesisCare - Adelaide Radiotherapy Centre
-
-
Victoria
-
Melbourne, Victoria, 호주
- Austin Health
-
Melbourne, Victoria, 호주
- Peter MacCallum Cancer Centre
-
-
Western Australia
-
Nedlands, Western Australia, 호주
- Sir Charles Gairdner Hospital
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion criteria
- 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
- Negative pregnancy test (for women of childbearing potential)
- Written informed consent.
Exclusion criteria
- Intra-cranial metastases (not meeting above inclusion criterion 8).
- 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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
활성 비교기: Standard of Care
Standard of care (SOC) is at the discretion of the local oncologist.
|
Choice of standard of care treatment at the discretion of the local oncologist.
This may include: Chemotherapy, Endocrine therapy, surgery, palliative radiotherapy
|
|
실험적: 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.
|
Choice of standard of care treatment at the discretion of the local oncologist.
This may include: Chemotherapy, Endocrine therapy, surgery, palliative radiotherapy
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.
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Progression Free Survival
기간: 60 months post treatment
|
Time from randomisation to evidence of progression of cancer at any site or death from any cause
|
60 months post treatment
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Feasibility of recruitment
기간: 3 years from first patient
|
Recruitment rate and proportion of patients receiving SBRT (if allocated) in the absence of new developing widespread disease
|
3 years from first patient
|
|
Feasibility of SBRT delivery
기간: 3 years from first patient
|
Recruitment of patients receiving SBRT within the dosimetric constraints
|
3 years from first patient
|
|
Overall Survival
기간: 60 months post treatment
|
Time from randomisation until time of death from any cause
|
60 months post treatment
|
|
Local lesion control
기간: 60 months post treatment
|
Time from randomisation until radiological evidence of progression at the treated site and be measured on a lesion based on analysis using RECIST criteria.
|
60 months post treatment
|
|
Clinical reported acute and late toxicity
기간: 60 months post treatment
|
Clinician reported acute and late toxicity will be graded using NCI CTCAE v4.0 / RTOG systems.
Acute events are defined as those occurring up to 3 months follow-up; late events are reported from 6 months post randomisation.
|
60 months post treatment
|
|
Patient reported Quality of Life
기간: Pre-treatment and at 3,6,12,18 and 24 months post treatment
|
Patient reported quality of life will be measured using EORTC QLQ C30
|
Pre-treatment and at 3,6,12,18 and 24 months post treatment
|
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Freedom from widespread metastatic disease (FFWMD)
기간: Pre-treatment and at 3,6,9,12,15,18,21,24,30,36,42,48,54 and 60 months post treatment
|
FFWMD will be measured from the time of randomisation until radiological evidence of disease progression, which is not suitable for radical salvage therapy.
|
Pre-treatment and at 3,6,9,12,15,18,21,24,30,36,42,48,54 and 60 months post treatment
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Vincent Khoo, MD, Royal Marsden NHS Foundation Trust
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (예상)
연구 완료 (예상)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
유방암에 대한 임상 시험
-
Georgetown UniversityNational Cancer Institute (NCI); American Cancer Society, Inc.; Susan G. Komen Breast Cancer...완전한
-
University of UtahNational Cancer Institute (NCI)완전한피로 | 좌식 생활 | 전이성 전립선암 | IV기 전립선암 AJCC(American Joint Committee on Cancer) v8 | IVA기 전립선암 AJCC(American Joint Committee on Cancer) v8 | IVB기 전립선암 AJCC(American Joint Committee on Cancer) v8미국
-
SB Istanbul Education and Research Hospital아직 모집하지 않음Thryoid cancer | parathyrıoid 선종
-
Jonsson Comprehensive Cancer CenterNovartis Pharmaceuticals모병전립선암 | IVB기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
-
Jonsson Comprehensive Cancer Center모병전립선 선암종 | 2기 전립선암 AJCC v8 | 1기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
-
Jonsson Comprehensive Cancer Center빼는전립선 선암종 | 2기 전립선암 AJCC v8 | IIC기 전립선암 AJCC v8 | IIA기 전립선암 AJCC v8 | IIB기 전립선암 AJCC v8 | 1기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
-
Jonsson Comprehensive Cancer CenterMiraDX모집하지 않고 적극적으로전립선 선암종 | 2기 전립선암 AJCC v8 | IIC기 전립선암 AJCC v8 | IIA기 전립선암 AJCC v8 | IIB기 전립선암 AJCC v8 | 1기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
-
Society for Endocrinology초대로 등록
-
Jonsson Comprehensive Cancer Center모병거세저항성 전립선암 | 전이성 전립선암 | IVA기 전립선암 AJCC v8 | IVB기 전립선암 AJCC v8 | IV기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
Standard of Care에 대한 임상 시험
-
Nebraska Methodist Health SystemAcera Surgical, Inc.종료됨
-
Pfizer완전한성인 혈우병 B 피험자(FIX:C≤2%) 또는 성인 혈우병 A 피험자(FVIII:C≤1%)에서 현재 FVIII 예방 대체 요법의 전향적 효능 및 안전성 데이터를 평가하기 위한 연구혈우병 A | 혈우병 B미국, 캐나다, 스페인, 호주, 대만, 브라질, 일본, 독일, 영국, 사우디 아라비아, 프랑스, 벨기에, 그리스, 이탈리아, 대한민국, 터키 (Türkiye), 이스라엘, 스웨덴
-
Compedica IncProfessional Education and Research Institute완전한
-
Kuros Biosurgery AG완전한당뇨성 족부궤양체코 공화국, 독일, 헝가리, 루마니아, 러시아 연방, 세르비아
-
ULURU Inc.Navy Advanced Medical Development (NAMD) Command모병
-
Occlutech International AB모집하지 않고 적극적으로뇌졸중 | 특허 구멍 타원형 | PFO미국, 덴마크, 캐나다, 프랑스, 영국, 네덜란드, 핀란드, 독일