Short-term radiotherapy versus chemoradiotherapy followed by consolidating chemotherapy and selective organ preservation for Patients with MRI-defined intermediate and high risk
- Conditions
- C20Malignant neoplasm of rectum
- Registration Number
- DRKS00020770
- Lead Sponsor
- Klinik für Strahlentherapie Universitätsklinikum Frankfurt/M
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 702
Male and female patients with histologically confirmed diagnosis of rectal adenocarcinoma, localized 0 - 12 cm from the anocutaneous line, measured by rigid rectoscopy (i.e. lower and
middle third of the rectum)
• Staging requirements: The high-resolution, Thin-slice (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
• MRI-Defined Inclusion Criteria: Presence at least one of the following high risk conditions:
• - each cT3 if the distal extent of the tumor <6 cm from the anocutaneous line, or
• - cT3c / d in the middle third of the rectum (= 6-12 cm) with MRI evidence of extramural spread Tumor in the mesorectal fat of more than 5 mm (> cT3b), or
• - cT3 with clear cN + based on strict MRI criteria (see appendix)
• cT4 tumors, or
• - each T middle / low third of the rectum with clear MRI criteria for N +
• - mrCRM + (= 1mm), or
• - Extramural venous invasion (EMVI +)
• Transrectal Endoscopic Ultrasound (EUS) is used additionally used if the MRI is not definitive, early cT1 / T2 disease in the lower third of the Rectum or early cT3a / b tumors in the middle third of the rectum to exclude Spiral CT of abdomen and chest to reveal distant metastases to exclude.
• At least 18 years old. No age limit.
• WHO / ECOG life status =1
• Adequate hematological, hepatic, renal and metabolic function parameters:
- leukocytes = 3,000 / mm ^ 3, ANC = 1,500 / mm ^ 3, Platelets = 100,000 / mm ^ 3, Hb> 9 g / dl
- Serum creatinine = 1.5 x upper limit of normal value
- Bilirubin = 2.0 mg / dl, SGOT-SGPT and AP = 3 x Upper limit of normal value
• Declaration of consent from the patient
The lower edge of the tumor is more than 12 cm from the anocutaneous line, measured through rigid rectoscopy
• Distant metastases (to be excluded by CT scan of Thorax and abdomen)
• Previous antineoplastic therapy for rectal cancer
• Prior radiotherapy to the pelvic region
• Major surgery within the last 4 weeks before the recording
• Pregnant or breastfeeding women or women who plan during the study or within up to 6 Getting pregnant months after completing your studies
• Men or women who are not too consistent Contraceptive measures with a reliable method during the study and up to 6 months after the end willing or able to study
• Simultaneous participation in a clinical study within 30 days of inclusion in the study
• Previous or current drug abuse
• Other concomitant antineoplastic therapy
• Serious concurrent illnesses, including neurological or psychiatric disorders (including dementia and uncontrolled seizures) more active, uncontrolled infections, more active, more disseminated Coagulation disorder
• Clinically significant cardiovascular disease (incl. Myocardial infarction, unstable angina pectoris, symptomatic heart failure, severe uncontrolled Cardiac arrhythmia) = 6 months prior to admission
• Previous or concurrent malignancy = 3 years ago Inclusion in the study (exception: non-melanoma skin cancer or cervical cancer FIGO stage 0-1), if the patient is continuously disease free Known allergic reactions to Study drugs
• Known deficiency in dihydropyrimidine dehydrogenase
• Psychological, familial, or sociological geographic conditions that may affect the Compliance with the study protocol and the Affect aftercare plan (these conditions should be used with the Patients are discussed).
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary endpoint of this study, organ preservation, is as follows defined: survival with an intact rectum, no major one Surgery, no stoma. The primary endpoint: organ preservation will not be reached if one of the following events occurs: Death, major surgery than local excision (R0), which after randomization, during TNT or during restaging in the 22nd to 24th week after the start of the TNT is carried out, due to the incomplete remmission or a locoregional growth after an initial, clinical Complete remission that requires a salvage TME, or a Stoma (non-reconverted protective stoma or stoma used for Toxicity or malfunction is required), depending on whichever comes first. We hypothesized that the 3-year organ retention rate increased from 30% in the control arm to 40% in the experimental arm will improve (hazard ratio of 0.76). At a power of 90% and a two-sided Type I error of 5% is the sample size required to obtain a statistically significant difference to get, a total of 702 Patients (564 events).
- Secondary Outcome Measures
Name Time Method Disease Free Survival<br>• Rate of complete clinical remissions after TNT<br>• Rate of immediate TME after TNT<br>• Cumulative incidence of locoregional after cCR<br>• Rate of salvage surgery rations (LE / TME with or without APR / stoma) after locoregional regrowth<br>• Cumulative incidence of local recurrences after (salvage) operations Postoperative complications of salvage surgery<br>• Rate of sphincter-sparing (salvage) operations<br>• Pathological TNM staging<br>• R0 resection rate, negative circumferential Resection rate<br>• Tumor regression grading according to Dworak<br>• Adjuvant rectal score<br>• Quality from TME according to MERCURY<br>• Assessment of acute and late toxicity according to NCI CTCAE V.5.0)<br>• Quality of life and functional outcome based on Treatment arm and surgical interventions / Organ preservation<br>• Cumulative incidence of distant metastases<br>• overall survival Translational / biomarker studies