A phase two randomised trial comparing organ preservation after Short course radiation Or Chemoradiation and Consolidation chEmotherapy in Rectal cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Difference between the Organ preservation rates in the two arms
研究概览
简要总结
The primary objective of this study is to compare the organpreservation potential of two neoadjuvant regimens (an escalated dosechemoradiation regimen or short course radiation followed by consolidationchemotherapy) in patients with LARC. Neoadjuvant chemoradiation followed by radicalsurgery is the standard practice for locally advanced low rectal cancer.However, surgery often leads to formation of a temporary or permanent stoma andis also associated with short term complications and long term bowel, sexualand urinary dysfunction leading to an impaired quality of life. In a recenttrial by the investigators, nearly 15% patients refused surgery afterneoadjuvant treatment. Total neoadjuvant therapy is increasingly being used inrectal cancer management and increases the tumor response rates. Patients whohave a complete response to neoadjuvant treatment have an excellent long termoutcome. Although a complete clinical response is not always concordant with acomplete pathological response, there is growing interest in a non-operativemanagement of patients who achieve a complete clinical response. The goodoncological outcome of this approach is supported by evidence from meta-analysesand publications from a large international registry. It has also been reportedthat patients who achieve a complete clinical response express a strongpreference to avoid surgery and are willing to trade life expectancy forimprovements in quality of life. Current organ preserving studies are focusingon an aggressive neoadjuvant long course chemoradiation regimen withconsolidation chemotherapy which has shown good results. Short course radiationfollowed by consolidation chemotherapy is also recommended in locally advancedrectal cancer but its role in organ preservation has not been studied. Hence weintend to compare the organ preserving potential of these two promisingregimens in a prospective clinical trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients must fulfil all of the following criteria to be considered eligible:
- •Histologically confirmed adenocarcinoma of the rectum 0-8 cm from anal verge
- •Age 18-70 years
- •ECOG performance status 0-2
- •MRI staged LARC deemed to require neoadjuvant radiation- Stage II (T3, N0) or Stage III (T1-3, N1-3)
- •Potentially resectable (amenable to total mesorectal excision)
- •No prior treatment for rectal cancer (chemotherapy or surgery or radiation)
- •Absolute neutrophil count > 1.5 cell/mm3, Hemoglobin>8.0 gm/ dL, Platelets> 150,000/mm3, total bilirubin ≤ 1.5 x upper limit of normal, AST ≤upper limit of normal, ALT≤ three times upper limit of normal, serum creatinine≤ 1.5 x upper limit of normal
- •Must have signed an informed consent form to participate in the study.
排除标准
- •Patients will not be eligible if they fulfil any of the following:
- •Presence of distant metastasis
- •Recurrent rectal cancer
- •Symptomatic bowel obstruction due to the tumor
- •Mucinous tumors or signet ring cell carcinoma
- •Familial adenomatous polyposis or hereditary non polyposis colorectal cancer
- •Have a contraindication for MRI e.g. non-MR compatible hip prosthesis, cardiac pacemaker
- •Patients who have received prior pelvic radiotherapy or have a contraindication to radiation
- •Patients who have any contraindication or hypersensitivity to the systemic chemo agents used in this study including but not limited to neuropathy, known DPD deficiency.
- •History of thrombotic arterial events eg.
- •stroke, myocardial infarction in the last 12 months or clinically significant cardiac disease or left ventricular ejection fraction <50%
- •Patients with any other concurrent uncontrolled medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study according to the investigator’s judgement.
- •Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
- •Patients receiving other anticancer or experimental therapy.
- •Patients who are pregnant, breastfeeding.
结局指标
主要结局
Difference between the Organ preservation rates in the two arms
时间窗: Difference between the Organ preservation rates in the two arms at two years from the completion of radiation.
次要结局
- Disease-free survival of patients in the NOM pathway(2 years from date of response assessment)
- Difference in the proportion of complete or near complete responses- (near) cCR- in the two treatment arms(24 weeks from completion of (chemo)radiation)
- Proportion of local regrowths in patients on NOM pathway(2 years from date of response assessment)
- Difference between the two arms in the proportion of Grade ≥3 30-day surgical complication measured by the Clavien-Dindo score(From day of surgery till 30 days post-operative)
- Difference between the two arms in the frequency of Grade ≥3 adverse events(During treatment- After completion of radiation and after each cycle of chemotherapy)
- Difference between the two arms in patient reported outcome measures(Time frame from randomisation till 2 years from response assessment)
- Difference in the compliance to consolidation chemotherapy between the two arms(From beginning of neoadjuvant treatment upto completion of (chemo) radiation.)
- Diagnostic performance of the pre-defined criteria for cCR and near cCR.(From response assessment to 12 months from decision for NOM].)