Randomised Phase II Trial to Evaluate Progression-Free Survival in Integrating Local Ablative Therapy With First-Line Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 18
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
This study aims to assess the clinical benefit of local ablative therapy (LAT) following initial standard first-line systemic treatment including the impact on survival, compared to continued standard first-line systemic treatment for oligometastatic colorectal cancer.
详细描述
Who is this study for:
Adults with unresectable oligo-metastatic colorectal who have demonstrated treatment benefit (partial response or stable disease as per RECIST criteria) after 3-4 months of standard first-line systemic treatment.
Study details
Participants will be randomly allocated to either a LAT arm, who will receive metastasis-directed LAT such as radiotherapy or thermal ablation following initial standard first-line systemic treatment, or a control arm who will receive continued first-line systemic treatment alone. Those receiving LAT will return to systemic treatment 16 weeks post-randomisation. Information on progression-free survival and treatment outcomes will be collected.
Data from this study will inform investigators of the potential benefit of local ablative therapy in the therapeutic setting for metastatic colorectal cancer.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Metastatic colorectal adenocarcinoma that is not amenable to potentially oncological curative surgery alone.
- •Primary tumour must be controlled if the primary is intact, with no evidence of progression at primary site prior to study entry
- •Imaging demonstrating ongoing treatment benefit (partial response or stable disease as per RECIST criteria) after 3-4 months of standard first-line systemic treatment.
- •At least one metastatic lesion detected on CT +/- FDG-PET scan prior to first line systemic treatment AND on screening FDG-PET and CT scans, meeting the following criteria:
- •max of 3 lesions per organ except for the liver and lung
- •max of 5 lesions in the lung
- •no limitation to the number of liver lesions provided they are all amenable to LAT
- •max of 3 involved organs including a lymph node station
- •only one lymph node station involvement is allowed
- •for patients with liver metastases, a quadruple phase contrast enhanced CT or MRI liver is required to fully stage the liver; this can be performed prior to or within 4 weeks of commencing first line systemic treatment
- •staging FDG-PET scan is encouraged and can be performed prior to or within 4 weeks of commencing first line systemic treatment
- •All lesions can be safely treated by LAT as determined by multidisciplinary team meeting.
排除标准
- •Deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-high) tumour
- •BRAFV600E mutated tumour
- •Concurrent or previous other malignancy within 2 years of study entry, except curatively treated basal or squamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, Bowen's disease or prostate cancer with a Gleason score ≤
- •Presence of brain, peritoneal, omental or ovarian metastases
- •Malignant pleural effusion or ascites.
研究组 & 干预措施
Local ablative therapies (LAT) arm
A maximum of three Local ablative therapy (LAT) modalities can be administered for each participant, with a maximum of 2 modalities per organ, provided all LAT can be delivered within 12 weeks and participant can safely resume systemic treatment within 16 weeks from randomisation.
After completing LAT, participant is to resume a further two to three months of first-line systemic treatment to a total of 6 months (including the initial 3-4 months of treatment). For patients receiving a doublet or triplet regimen, treatment may be de-escalated to maintenance fluoropyrimidine +/- biologics or anti-EGFR monotherapy at any point after trial entry at clinician discretion. The treating clinician may choose to discontinue systemic treatment following LAT for patients who have experienced prior intolerable toxicity.
干预措施: Local Ablative Therapy (Procedure)
Local ablative therapies (LAT) arm
A maximum of three Local ablative therapy (LAT) modalities can be administered for each participant, with a maximum of 2 modalities per organ, provided all LAT can be delivered within 12 weeks and participant can safely resume systemic treatment within 16 weeks from randomisation.
After completing LAT, participant is to resume a further two to three months of first-line systemic treatment to a total of 6 months (including the initial 3-4 months of treatment). For patients receiving a doublet or triplet regimen, treatment may be de-escalated to maintenance fluoropyrimidine +/- biologics or anti-EGFR monotherapy at any point after trial entry at clinician discretion. The treating clinician may choose to discontinue systemic treatment following LAT for patients who have experienced prior intolerable toxicity.
干预措施: Standard first-line systemic treatment (Procedure)
Control arm
The first-line systemic treatment will be standard of care as determined by the treating clinician. The following standard chemotherapy regimens are allowed: single agent fluoropyrimidine, CAPOX, FOLFOX, FOLFIRI, CAPIRI or FOLFOXIRI. Treatment with a biologic is allowed including bevacizumab or an anti-EGFR antibody (cetuximab or panitumumab). For patients receiving a doublet or triplet regimen, treatment may be de-escalated to maintenance fluoropyrimidine +/- biologics or anti-EGFR monotherapy at any point after trial entry at clinician discretion.
干预措施: Standard first-line systemic treatment (Procedure)
结局指标
主要结局
Progression free survival (PFS)
时间窗: 12 Months from randomisation
To compare the efficacy of metastasis-directed LAT following initial standard first-line systemic treatment vs continued first-line systemic treatment alone, as measured by Progression-Free Survival (PFS)
次要结局
- Rate of high-grade toxicities(Through study completion, an average of 1 year)
- Efficacy of local ablative therapy(12 Months from randomisation and through study completion, an average of 1 year)
- Time to progression following local ablative therapy(Through study completion, an average of 1 year)
- Systemic treatment-free interval(Through study completion, an average of 1 year)
- Quality of life measure(Through study completion, an average of 1 year)
- Overall survival(12 Months from randomisation and through study completion, an average of 1 year)