A Multicenter Phase II Randomized Trial to Evaluate Systemic Therapy Versus Systemic Therapy in Combination with Stereotactic Radiotherapy in Patients with Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 发起方
- UMC Utrecht
- 入组人数
- 93
- 试验地点
- 4
- 主要终点
- Progression-free survival
研究概览
简要总结
A small number of colorectal cancer patients with limited oligometastases may be candidates for local treatment of metastases (e.g., resection, ablation). However, it is unclear if patients with more extensive metastatic disease benefit from local therapies to control visible metastasis.
The purpose of this study is to assess the impact of stereotactic body radiation therapy (SBRT) in combination with systemic therapy compared to systemic therapy alone on safety and efficacy in patients with metastatic colorectal cancer (mCRC) and ≤10 metastases.
详细描述
The addition of stereotactic body radiation therapy (SBRT) to metastases in a limited unresectable metastatic setting might improve progression-free survival (PFS). The success of the addition of local treatments in mCRC patients depends largely on: control of microscopic disease, diagnostic accuracy of macroscopic disease and effective treatment of all detected metastases with limited additional toxicity to surrounding tissues. Until shortly, the use of SBRT was possible to a limited number of locations due to target movement or toxicity to surrounding radiosensitive structures. With the introduction of MRI-guided radiotherapy these limitations have been largely reduced due to the possibility to make a daily new treatment plan based on MRI-visualized anatomy. This allows the use of smaller margins for uncertainty with less healthy tissues in the radiation field. Thereby, a broader application of SBRT to add local control to metastases became possible.
This study is an open-label, multicenter, randomized phase II screening trial assessing the impact of SBRT in combination with systemic therapy compared to systemic therapy alone on safety and efficacy in patients with mCRC and ≤10 metastases with no option of local treatment with curative intent and with stable disease or partial response after treatment of CAPOX-B, FOLFOX-B or FOLFOXIRI-B.
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
- •Registered in the prospective Dutch colorectal cancer cohort (PLCRC)
- •Intention at start of palliative systemic therapy to receive six maximum tolerated dose (MTD) cycles of CAPOX-B or eight MTD cycles of FOLFOX-B or FOLFOXIRI-B.
- •Ten or less metastases as determined by the university medical center Utrecht (UMCU) central review
- •Stable disease or partial response after initial chemotherapy according to RECIST 1.1 criteria.
- •Expected adequacy of follow-up
- •World Health organization (WHO) performance status 0-1
- •Life expectancy >12 weeks
- •Adequate organ functions at start of initial therapy, as determined by normal bone marrow function (Hb≥6.0 mmol/L, absolute neutrophil count ≥1.5 x 10^9/L, platelets ≥100 x 10^9/L), renal function (serum creatinine ≤ 1.5x upper limit of normal (ULN) and creatinine clearance, Cockcroft formula, ≥30 ml/min) and liver function (serum bilirubin ≤ 2 x ULN, serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases)
- •Written informed consent (SIRIUS)
排除标准
- •Less than three cycles of CAPOX-B or four cycles of FOLFOX-B or FOLFOXIRI-B (dose reductions allowed).
- •More than six cycles of CAPOX-B or eight cycles of FOLFOX-B of FOLFOXIRI-B.
- •Possible treatment with curative intent according to local tumor board
- •Substantial overlap with a previously treated radiation volume. Previous radiotherapy is allowed as long as the composite plan meets dose constraints herein.
- •Not amenable for radiotherapy (e.g. peritonitis carcinomatosa)
- •Previous systemic treatment for metastatic disease; prior adjuvant treatment for stage II/III colorectal cancer when given >6 months before the start of initial systemic treatment is allowed.
- •Serious comorbidity or any other condition preventing the safe administration of treatment (including both systemic treatment and radiation)
- •Pregnant or lactating women
- •Other malignancy interfering with prognosis
- •Any concomitant experimental treatment.
- •Contra-indication MR-LINAC (pacemaker or implantable cardioverter-defibrillator)
- •Microsatellite instability or deficient mismatch repair tumor
研究组 & 干预措施
Systemic maintenance therapy
干预措施: Maintenance therapy (CAP-B or 5-FU/LV plus bevacizumab.) (Drug)
Systemic maintenance therapy in combination with stereotactic body radiation therapy (SBRT)
干预措施: Stereotactic body radiation therapy (SBRT) (Radiation)
Systemic maintenance therapy in combination with stereotactic body radiation therapy (SBRT)
干预措施: Maintenance therapy (CAP-B or 5-FU/LV plus bevacizumab.) (Drug)
结局指标
主要结局
Progression-free survival
时间窗: Through study completion, an average of 24 months
Defined as time from randomization to progression of disease or death, whichever occurs first. Progression of disease is based on tumor response as observed on radiographic imaging according to the RECIST 1.1 criteria.
次要结局
- Accrual rate as assessed by the number of patients included in the study compared to the expected accrual rate.(Through study completion, an average of 24 months)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(Through study completion, an average of 24 months)
- Overall survival(Up to 72 months)
- Comparing changes on health-related quality of life based on summary score of Quality of Life Questionnaire-Core30 (QLQ-C30) from baseline and 3-monthly timepoints.(Through study completion, an average of 24 months)
- Comparing changes on health-related quality of life based on summary score of Quality of Life Questionnaire-Core29 (QLQ-C29) from baseline and 3-monthly timepoints.(Through study completion, an average of 24 months)
- Pattern of reccurence according to RECIST 1.1: New metastatic lesions, progression of existing lesions or a combination.(Through study completion, an average of 24 months)
- Comparing changes from health-related quality of life based on summary score of Multidimensional Fatigue Inventory (MFI-20) from baseline and 3-monthly timepoints.(Through study completion, an average of 24 months)
- Time to treatment failure(Through study completion, an average of 24 months)
- Tumor response(Through study completion, an average of 24 months)
- Depth of response(Through study completion, an average of 24 months)
- Treatment success rate(Through study completion, an average of 24 months)