STAR-TREC: Can we Save the Rectum by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 380
- 试验地点
- 5
- 主要终点
- Phase III Primary Outcome: Organ Preservation
研究概览
简要总结
Bowel cancer is the second most common tumour with 41 000 new cases diagnosed annually in the UK, 447 000 across Europe and 1.36 million worldwide; of which one third are located in the rectum. Standard primary radical Total Mesorectal Excision (TME) surgery is an oncologically effective treatment for early stage rectal cancer. However, resection of a low rectal tumour requires a permanent stoma in approximately 10% of cases while many more patients have a temporary stoma, some of which are not reversed. Radical surgery, which evolved to treat locally advanced, symptomatic tumours, may not be the optimal method of treatment for early screen-detected tumours and an organ preserving strategy may generate significantly less morbidity without substantially compromising oncological outcomes.
STAR-TREC is a rolling phase II/III study. Phase II aimed to assess the feasibility of a large, multi-centre randomised trial comparing radical surgery versus two contrasting organ saving treatments followed by selective transanal microsurgery. Phase III will evaluate two contrasting organ preservation strategies in terms of organ preservation rates, toxicity (clinician and patient-reported) and Health-Related Quality of Life (HRQoL).
详细描述
The Phase II component of STAR-TREC (now completed) was a randomised, three arm (1:1:1) study using the following arms:
-
Standard TME surgery (control)
-
Organ saving treatments using:
-
Long course concurrent chemoradiation:
- Capecitabine: 825 mg/m² orally, b.d., on radiotherapy days
- Radiotherapy: A dose of 50 Gy applied to the primary tumour and surrounding mesorectum in 25 fractions of 2 Gy, 5 days a week.
- Short course radiotherapy:
- A dose of 25 Gy applied to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Biopsy proven adenocarcinoma of the rectum
- •MRI-defined ≤T3b (with ≤5mm of mesorectal invasion) rectal tumour or endorectal ultrasound-defined ≤uT3b rectal cancer (optional: in centres where high quality endorectal ultrasound (ERUS) is available or patient unable to tolerate MRI)
- •MDT determines that all of the following treatment options are reasonable and feasible:
- •-TME surgery, (b) CRT (c) SCRT d) TEM.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •For patients choosing organ preservation only:
- •If female and of childbearing potential, must:
- •Have a negative pregnancy test within 7 days prior to study entry
- •Agree to use adequate, medically approved, contraceptive precautions from trial entry until 6 months after the end of study treatment
- •If non-sterilised male male with a partner of childbearing potential, must:
- •Agree to use adequate, medically approved, contraceptive precautions from trial entry until 6 months after the end of study treatment
- •Patient able and willing to provide written informed consent for the study
排除标准
- •Concomitant or previous malignancies within 3 years prior to trial entry, except those that in the opinion of the MDT are unlikely to relapse within 3 years or lead to death within 5 years
- •Unequivocal evidence of metastatic disease (includes resectable metastases)
- •-- Patients with equivocal radiological lesions (e.g. retroperitoneal, liver, lung) that are not classified as M1 are eligible if agreed by MDT
- •MRI node positive (≥N1, defined by protocol guidelines)
- •-- Patients with equivocal radiological findings that are either classified as NX or N0 are eligible
- •MRI extramural vascular invasion (mriEMVI) positive (defined by protocol guidelines)
- •MRI defined mucinous tumour
- •Mesorectal fascia threatened (≤1 mm on MRI or ERUS)
- •Maximum tumour diameter > 40mm (either measured from everted edges on sagittal MRI or on ERUS)
- •Tumour position anterior, above the peritoneal reflection on MRI or EUS
- •No residual luminal tumour following endoscopic resection
- •Contraindications to radiotherapy including previous pelvic radiotherapy
- •Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction or arrhythmia within 6 months prior to trial entry)
- •Known complete dihydropyrimidine dehydrogenase (DPYD) deficiency
- •Known Gilbert's disease (hyperbilirubinaemia)
- •Taking coumarin-derivative anticoagulants (e.g. warfarin) that cannot be discontinued at least 7 days prior to starting treatment or substituted by low molecular weight heparin
- •Taking phenytoin or sorivudine or its chemically related anologues, such as brivudine, within 4 weeks of trial entry (see Section 8.3.5 for further details)
- •Taking metronidazole at study entry
- •Pregnant or lactating women
- •History of severe and unexpected reactions to fluoropyrimidine therapy
- •Age <16 years (UK), <18 years (other countries)
研究组 & 干预措施
Long course concurrent chemoradiation
Capecitabine: 825 mg/m² orally, b.i.d., on radiotherapy days Radiotherapy: A dose of 50 Gy, applied to the primary tumour and surrounding mesorectum, in 25 fractions of 2 Gy, 5 days a week.
干预措施: Long course concurrent chemoradiation with capecitabine and radiotherapy (Drug)
Short course radiotherapy
A dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week.
干预措施: Short course radiotherapy (Radiation)
Standard TME surgery
Radical total mesorectal excision
干预措施: Standard TME surgery (Procedure)
结局指标
主要结局
Phase III Primary Outcome: Organ Preservation
时间窗: 30 Months from start day of (chemo)radiotherapy treatment.
The primary endpoint of the STAR-TREC phase III study is the proportion of patients with successful organ preservation at 30 months from the start day of (chemo)radiotherapy treatment. This endpoint will be assessed for patients who prefer organ preservation and is defined as an in-situ rectum (includes patients subject to transanal local resection), no defunctioning stoma and an absence of active loco-regional cancer failure. The expected incidence of this outcome is approximately 60%.
Phase II (Feasibility study) Primary Outcome: Recruitment Rate
时间窗: 24 Months
Measured at 12 and 24 months. Target recruitment rates are ≥4 and ≥6 patients randomised per month at 12 and 24 months respectively for total accrual of 120 international cases. Each individual country will attempt to exceed the minimum recruitment required to sustain phase III (UK 75, the Netherlands 75, Denmark 30). If recruitment is on target in year two then consideration will be given to an early application for transition to phase III with a funding application and a formal protocol amendment.
次要结局
- Phase II: Safety- Accuracy of MRI in predicting STAR-TREC eligibility(24 Months)
- Phase II (Feasibility study): Core Endpoint - Funding(12 Months)
- Phase II: Safety - 6 month Mortality(6 Months)
- Phase II: Safety - Surgical Morbidity(36 Months)
- Phase II: Safety - Distant Metastasis(36 Months)
- Phase II: Efficacy - Disease Survival(36 Months)
- Phase II: Efficacy - Conversion Rate(36 Months)
- Phase III: For the randomised comparison between organ-preserving strategies - Non-regrowth Disease Free Survival(36 months)
- Phase III: For analyses incorporating the non-randomised standard surgery comparator - Toxicity(30 days)
- Phase III: For the randomised comparison between organ-preserving strategies - Overall Survival(60 months)
- Phase III: For analyses incorporating the non-randomised standard surgery comparator - Overall Survival(60 months)
- Phase III: For analyses incorporating the non-randomised standard surgery comparator - Decision Regret(24 months)
- Phase III: For analyses incorporating the non-randomised standard surgery comparator - Disease-free Survival(36 months)
- Phase II (Feasibility study): Core Endpoint - Efficacy(12 Months)
- Phase II: Safety - Tumour Recurrence within Mesorectum(36 Months)
- Phase II: Efficacy - Active Monitoring(4.5 Months)
- Phase II: Efficacy - Overall Survival(36 Months)
- Phase II: Safety - 30 day Mortality(30 days)
- Phase II: Safety - Tumour Recurrence/ Regrowth within Bowel Wall(36 Months)
- Phase II: Safety - Pelvic Failure(36 Months)
- Phase II: Efficacy - Stoma(24 Months)
- Phase II: Efficacy - Tumour Down-staging(4.5 Months)
- Phase II: Efficacy - Health-related Quality of Life score(3 months)
- Phase II: Efficacy - Health-related Quality of Life score(12 Months)
- Phase II: Efficacy - Health-related Quality of Life score(24 Months)
- Phase II: Safety - Bowel(36 Months)
- Phase II: Safety - Bladder(36 Months)
- Phase II: Safety - Sexual dysfunction(36 Months)
- Phase II: Efficacy - Health-related Quality of Life score(36 Months)
- Phase III: Complete Response *For the randomised comparison between organ-preserving strategies(30 months)
- Phase III: For the randomised comparison between organ-preserving strategies - Local Excision(20 weeks)
- Phase III: For analyses incorporating the non-randomised standard surgery comparator - Non-regrowth Pelvic Tumour Control(36 months)
- Phase III: For the randomised comparison between organ-preserving strategies - Non-Regrowth(36 months)
- Phase III: For the randomised comparison between organ-preserving strategies - Metastasis Free Survival(36 months)
- Phase II (Feasibility study): Core Endpoint - International Recruitment(12 Months)
- Phase III: For the randomised comparison between organ-preserving strategies(30 days from start day of (chemo)radiotherapy treatment.)
- Phase III: For the randomised comparison between organ-preserving strategies - Organ Loss(Defined as the length of time from the start date of trial treatment until TME surgery)
- Phase III: For analyses incorporating the non-randomised standard surgery comparator - Metastasis Free Survival(36 months)