2024-511577-29-01招募中3 期
Short course radiotherapy versus chemoradiotherapy, followed by consolidation chemotherapy, and selective organ preservation for MRI-defined intermediate and high-risk rectal cancer patients, A randomized phase III trial of the German Rectal Cancer Study Group
Goethe University Frankfurt66 个研究点 分布在 1 个国家目标入组 688 人开始时间: 2024年9月26日最近更新:
适应症
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 688
- 试验地点
- 66
- 主要终点
- The primary endpoint of this trial, organ preservation, is defined as follows: survival with rectum intact, no major surgery, no stoma.
研究概览
简要总结
The primary endpoint of this trial, organ preservation, is defined as follows: survival with rectum intact, no major surgery, no stoma. Accordingly, the primary endpoint, organ preservation, will not be reached if any of the following occurs: (1) death, (2) any major surgery other than local excision (R0) performed after randomization, during TNT, at re-staging scheduled 22-24 weeks after start of TNT due to clinical non-cCR, or for any locoregional regrowth after initial cCR requiring salvage-TME, (3) any locoregional regrowth not amenable to salvage surgery, or (4) any stoma (non-re-converted protective stoma within 6 months after completion of TNT, or any stoma needed for toxicity or poor function), whichever occurs first. We hypothesized that the 3-year organ preservation rate will improve from 30% in the control arm to 40% in the investigational arm (hazard ratio of 0.76). With a power of 90% and a two-sided type I error of 5%, the sample size required to obtain a statistically significant difference is 702 patients (564 events) in total.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Male and female patients with histologically confirmed diagnosis of rectal adenocarcinoma localised 0 – 12 cm from the anocutaneous line as measured by rigid rectoscopy (i.e. lower and middle third of the rectum).
- •Staging requirements: High-resolution, thin-sliced (i.e. 3 mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
- •MRI-defined inclusion criteria: presence of at least one of the following high-risk conditions: any cT3 if the distal extent of the tumor is < 6 cm from the anocutaneous line, or cT3c/d in the middle third of the rectum (≥ 6-12 cm) with MRI evidence of extramural tumor spread into the mesorectal fat of more than 5 mm (>cT3b), or cT3 with clear cN+ based on strict MRI-criteria (see appendix) cT4 tumors, or Tany middle/low third of rectum with clear MRI criteria for N+, mrCRM+ (≤1mm), or Extramural venous invasion (EMVI+).
- •Transrectal endoscopic ultrasound (EUS) is additionally used when MRI is not definitive to exclude early cT1/T2 disease in the lower third of the rectum or early cT3a/b tumors in the middle third of the rectum.
- •Spiral-CT of the abdomen and chest to exclude distant metastases.
- •Aged at least 18 years. No upper age limit.
- •WHO/ECOG Performance Status ≤
- •Adequate haematological, hepatic, renal and metabolic function parameters: Leukocytes ≥ 3.000/mm3 , ANC ≥ 1.500/mm3 , platelets ≥ 100.000/mm3 , Hb > 9 g/dl. Serum creatinine ≤ 1.5 x upper limit of normal. Bilirubin ≤ 2.0 mg/dl, SGOT-SGPT, and AP ≤ 3 x upper limit of normal.
- •Informed consent of the patient.
排除标准
- •Lower border of the tumor localised more than 12 cm from the anocutaneous line as measured by rigid rectoscopy.
- •Other concomitant antineoplastic therapy.
- •Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder.
- •Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 6 months before enrolment.
- •Prior or concurrent malignancy ≤ 3 years prior to enrolment in study (Exception: non- melanoma skin cancer or cervical carcinoma FIGO stage 0-1), if the patient is continuously disease-free.
- •Known allergic reactions on study medication.
- •Known dihydropyrimidine dehydrogenase deficiency (activity score < 1,5 after genetic testing of DPYD variants)
- •Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (these conditions should be discussed with the patient before registration in the trial).
- •Distant metastases (to be excluded by CT scan of the thorax and abdomen).
- •Prior antineoplastic therapy for rectal cancer.
- •Prior radiotherapy of the pelvic region.
- •Major surgery within the last 4 weeks prior to inclusion.
- •Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
- •Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly).
- •On-treatment participation in a clinical study in the period 30 days prior to inclusion.
- •Previous or current drug abuse.
结局指标
主要结局
The primary endpoint of this trial, organ preservation, is defined as follows: survival with rectum intact, no major surgery, no stoma.
The primary endpoint of this trial, organ preservation, is defined as follows: survival with rectum intact, no major surgery, no stoma.
次要结局
- Rate of clinical complete response after TNT
- Pathological TNM-staging
- Overall survival
- Rate of immediate TME after TNT
- Cumulative incidence of locoregional regrowth after cCR
- Disease-free survival
- Rate of salvage surgery (LE/TME with or without APR/stoma) after locoregional regrowth
- Cumulative incidence of local recurrence after (salvage) surgery
- Postoperative complications of (salvage) surgery
- Rate of sphincter-sparing (salvage) surgery
- R0 resection rate; negative circumferential resection rate
- Tumor regression grading according to Dworak
- Neoadjuvant rectal score
- Quality of TME according to MERCURY
- Acute and late toxicity assessment according to NCI CTCAE V.5.0)
- Quality of life and functional outcome based on treatment arm and surgical procedures/organ preservation
- Cumulative incidence of distant metastases
- Translational / biomarker studies
研究者
Atefeh Nateghian
Scientific
Goethe University Frankfurt
研究点 (66)
Loading locations...
相似试验
已完成
2 期
Organ Preservation Program Using Short-Course Radiation & FOLFOXIRI in Rectal CancerRectal CancerNCT04380337Stanford University38
Unknown
不适用
Radiotherapy vs Observation for CRPCHormone Refractory Prostate CancerNCT01590498Zhengzhou University2,000
招募中
2 期
Chemoradiation therapy on conversion surgery for unresectable locally advanced pancreatic cancerPancreatic ductal adenocarcinomaUnresectable locally advenced pancreatic cancer, Prospective randomized control study, Chemoradiotherapy, Conversion surgeryD021441JPRN-jRCTs051210167Kobayashi Shogo70
招募中
2 期
The Efficacy and Safety of Short-course Radiation Combined With Adebrelimab and CAPEOX Neo-adjuvant Therapy for Organ-retention in Patients With MSS/pMMR Ultra Low Rectal AdenocarcinomaRectal AdenocarcinomaNCT06266832Sir Run Run Shaw Hospital30
招募中
2 期
Modified Long-Course Radiotherapy Followed by Chemotherapy and PD-1 Inhibitor for MSS/pMMR High-risk Mid/Low LARC (MODIFI-RC-I)Rectal CancerImmune Checkpoint TherapyNeoadjuvant TherapiesRadiotherapyNCT06923345Sixth Affiliated Hospital, Sun Yat-sen University80