Forschung

ACO/ARO/AIO-18.1

Organ preservation in locally advanced rectal cancer by radiochemotherapy followed by consolitadion chemotherapy. A prospective Phase II Pilot Trial of the German Rectal Cancer Group  CAO/ARO/AIO-16

Study type: Investigator-driven, multicenter, open, prospective phase II study

 

Population: Patientens with local advanced rectal cancer cUICC (Phase II-III)

 

Primary objective: The primary objective of the study is to estimate the effect of radiochemotherapy followed by consolidation chemotherapy in locally advanced rectal cancer. As primary endpoint, the rate of patients with a clinical complete response (cCR) will be determined. This rate will then be the basis for patient number calculations in a consecutive trial with 3-year loco-regional control as endpoint.

 

Sekundary objectives:

• Local regrowth rat
• Safety of the treatment (toxicity assessment according to NCI CTCAE Version 4.0)
• Fecal incontinence according to Wexner-Vaizey Score
• Quality of life according to EORTC QOL-C30 and QOL-CR29
• Frequency of Low anterior resection syndrome (LARS-scale)
• Surgical morbidity and complications in patients undergoing surgery
• Pathological staging, tumor downstaging (assessed by ypTNM findings in relation to initial cTNM staging), tumor regression grading according to Dworak in patients undergoing surgery
• R0 resection rate, rate of circumferential resection margin negativity (> 1mm) in patients undergoing surgery
• Rate of sphincter-sparing surgery in patients undergoing surgery
• Relapse-free survival (local / distant / overall)
• Overall survival
• Translational biomarker studies

Inclusion criteria:

• Male and female patients with histologically confirmed diagnosis of rectal cancer localized 0 – 12 cm from the anocutaneous line as measured by rigid rectoscopy (i.e. lower and middle third of the rectum)
• Any MRI staged cT3 tumor or any cT1 cN+ or cT2 cN+ with nodal staging according to “SOP MRI”
• Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
• Cross-sectional imaging of the abdomen and chest to exclude distant metastases.
• Aged at least 18 years. No upper age limit.
• WHO/ECOG Performance Status ≤ 1
• Informed consent of the patient
• 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
  - Creatinin-Clearance ≥ 30 ml / min
  - Bilirubin ≤ 2.0 mg/dl, SGOT-SGPT, and AP ≤ 3 x upper limit of norm

Exclusion criteria:

• Lower border of the tumor localised more than 12 cm from the anocutaneous line as measured by rigid rectoscopy
• cT4 tumors
• Positive lateral pelvic lymph nodes (s. SOP MRI)
• Distant metastases (to be excluded by CT scan of the thorax and abdomen)
• Preexisting fecal incontinence for solid stool
• Preexisting peripheral sensory neuropathy with functional impairment
• Preexisting myelosuppression refleted by a neutrophil count < 2.000/mm^3 and/or platelets < 100.000/mm^3
• Severe impairment of kidney function with a Creatinin Clearance < 3 ml/min)
• 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 according to the “Clinical trial fertility group” recommendations during treatment and for 6 months (male or female) after the end of Treatment
• On-treatment participation in an interventional clinical study in the period 30 days prior to inclusion
• Previous or current drug abuse
• Other concomitant antineoplastic therapy
• Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder
• WHO/ECOG Performance Status > 1
• Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 6 months before enrolment
• Chronic diarrhea (> grade 1 according NCI CTCAE)
• 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
• Medication inhibitors of the dihydropyrimidine dehydrogenase, such as Brivudin, Sorivudin and its analogues
• Pernicious anemia or other anemias caused by Vitamin B-12 deficiency
• 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)
• Additionally for hyperthermia cardiac pacemakers and metal implants in the proximity of the pelvis constitute a criterion for exclusion