CAO/ARO/AIO-16

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