Neo-adjuvant FOLFOXIRI and Chemoradiotherapy for High Risk ("Ugly") Locally Advanced Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 128
- 试验地点
- 7
- 主要终点
- The main study parameter is the proportion of patients with a pathological complete response (pCR) and those patients who started a wait and see strategy and have sustained clinical complete response (cCR) at 1 year.
研究概览
简要总结
Despite developments in the multidisciplinary treatment of patients with locally advanced rectal cancer (LARC), such as the introduction of total mesorectal excision (TME) by Heald et al. and the shift from adjuvant to neoadjuvant (chemo)radiotherapy ((C)RT), local and distant recurrence rates remain between 5-10% and 25-40% respectively. Several studies established tumour characteristics with particularly bad prognosis; it was demonstrated that the occurrence of mesorectal fascia involvement (MRF+), grade 4 extramural venous invasion (EMVI), tumour deposits (TD) and enlarged lateral lymph nodes (LLN) lead to high local and distant recurrence rates and decreased survival when compared with LARC without these particularly negative prognostic factors. This type of LARC is described as high risk LARC (hr-LARC). Achieving a resection with clear resection margins (R0) is an important prognostic factor for local (LR) and distant recurrence (DM) as well as survival. With the aim to further reduce the risk of recurrent rectal cancer, to diminish distant metastasis and to improve overall survival for patients with LARC, induction chemotherapy (ICT) became a growing area of research. The addition of ICT has the ability to induce more local tumour downstaging, possibly leading to resectability of previously unresectable tumours, more R0 resections and less extensive surgery. In the case of a complete clinical response, surgery may even be omitted. ICT may also have the potential to eradicate micrometastases. Hence, increased local downstaging and reducing distant metastatic spread may reduce LR and DM rates and improve survival and quality of life. In recent years, the use of ICT was investigated and showed promising results, but little is known about the addition of ICT in patients with high risk LARC. Since these patients have a particularly bad prognosis, both with regard to locoregional and distant failure, a more intensified neoadjuvant treatment with FOLFOXIRI is anticipated to improve short- and long term results.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •18 years or older
- •WHO performance score 0-
- •Histopathologically confirmed rectal cancer.
- •Lower border of the tumour located below the sigmoidal take-off as established on MRI of the pelvis.
- •Confirmed high-risk locally advanced rectal cancer, meeting one of the following imaging based criteria:
- •Tumour invasion of mesorectal fascia (MRF+)
- •The presence of grade 4 extramural venous invasion (mrEMVI)
- •The presence of tumour deposits (TD)
- •The presence of Extramesorectal lymph nodes with a short-axis size > 7mm (LNN)
- •Resectable disease as determined on magnetic resonance imaging (MRI) or deemed resectable disease after neoadjuvant treatment.
- •Expected gross incomplete resection with overt tumour remaining in the patient after resection, tumour invasion in the neuroforamina, encasement of the ischiadic nerve and invasion of the cortex from S3 and upwards are considered not resectable • Written informed consent.
排除标准
- •Evidence of metastatic disease at the moment of inclusion or within six months prior to inclusion except for patients with enlarged iliac or inguinal lymph nodes and aspecific lung noduli.
- •Homozygous DPD (Dihydropyrimidine dehydrogenase) deficiency.
- •Any chemotherapy within the past 6 months.
- •o Any contraindication for the planned systemic therapy (e.g. severe allergy, pregnancy, kidney dysfunction and thrombocytopenia), as determined by the medical oncologist.
- •Radiotherapy in the pelvic area within the past 6 months.
- •Any contraindication for the planned chemoradiotherapy (e.g. severe allergy to the chemotherapy agent or no possibility to receive radiotherapy), as determined by the medical oncologist and/or radiation oncologist.
- •Any contraindication to undergo surgery, as determined by the surgeon and/or anaesthesiologist.
- •Concurrent malignancies that interfere with the planned study treatment or the prognosis of the resected tumour.
研究组 & 干预措施
Single-arm study
All patients will receive induction chemotherapy consisting of 4-6 cycles of FOLFOXIRI. Restaging will be performed after 4 cycles with a pelvic MRI and a thoraco-abdominal CT-scan. In case of stable or responsive disease, the remaining 2 cycles of FOLFOXIRI will be provided. In case of progressive, but still resectable disease, chemoradiation will be provided immediately, without the remaining 2 cycles of FOLFOXIRI. Restaging will be performed after chemoradiation. In case of resectable disease, surgery is performed.
干预措施: FOLFOXIRI Protocol (Drug)
结局指标
主要结局
The main study parameter is the proportion of patients with a pathological complete response (pCR) and those patients who started a wait and see strategy and have sustained clinical complete response (cCR) at 1 year.
时间窗: pCR is determined after surgery directly. There is a cCR in case of a sustained clinical response until at least one year after chemoradiotherapy
The pCR is evaluated by an experienced pathologist. A pCR is defined as the absence of residual tumour cells in the complete resected specimen including all resected regional lymph nodes (ypT0N0). A cCR is defined as the absence of viable tumour tissue based on MRI, evaluated by an experienced radiologist. There is a cCR in case of a sustained clinical response at 1 year after chemoradiotherapy.
次要结局
- 3-year and 5-year local recurrence free survival.(3 and 5 year)
- 3-year and 5-year distant metastasis free survival.(3 and 5 year)
- 3-year and 5-year progression free survival.(3 and 5 year)
- 3-year and 5-year disease free survival.(3 and 5 year)
- 3-year and 5-year overall survival.(3 and 5 year)
- Radiological response after induction therapy.(Directly after induction chemotherapy)
- Radiological response after chemoradiotherapy.(6-8 weeks after chemoradiotherapy)
- Pathologic response(Directly after surgery)
- Toxicity related to induction therapy.(During induction chemotherapy)
- The induction therapy compliance rate.(During induction chemotherapy)
- Toxicity of chemoradiotherapy.(During chemoradiotherapy)
- The compliance rate related to chemoradiotherapy.(During chemoradiotherapy)
- Number of patients undergoing surgery.(immediately after surgery)
- Type of surgery, including the use of intra-operative radiotherapy.(During the surgical procedure)
- Major surgical morbidity rate(During admission for surgery.)
- Generic and cancer-specific Quality of life (QoL) assessments during treatment using Quality of life Questionnaires (QLQ)(At the moment of inclusion, after 3 months and after 12 months.)
- Generic and cancer-specific Quality of life (QoL) assessments during treatment(At the moment of inclusion, after 3 months and after 12 months.)
- Costs(At the moment of inclusion, after 3 months and after 12 months.)
研究者
J. W. A. Burger
Principal investigator
Catharina Ziekenhuis Eindhoven