Locally advanced rectal cancer (UICC stage II and III) MedDRA version: 21.0 Level: PT Classification code 10038050 Term: Rectal cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10038049 Term: Rectal cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OXALIPLATIN
CAS Number: 61825-94-3
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: FLUOROURACIL
Other d
Sponsors
University Hospital Frankfurt, Goethe University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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. 3mm) 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 cT3b), or - resectable cT4 tumors, or - any clear cN+ based on MRI-criteria (see appendix) • Trans-rectal 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 =1 • Adequate haematological, 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 - Bilirubin = 2.0 mg/dl, SGOT-SGPT, and AP = 3 x upper limit of normal • Informed consent of the patient Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 304 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 304
Exclusion criteria
Exclusion criteria: • Lower border of the tumor localised more than 12 cm from the anocutaneous line as measured by rigid rectoscopy • 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 • On-treatment participation in a clinical study in the period 30 days prior to inclusion • Previous or current drug abuse • Concomitant other antineoplastic therapy • Serious concomitant 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. • 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 • Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the efficacy of induction chemotherapy followed by chemoradiotherapy, or the other way round, before surgery in patients with locally advanced rectal cancer. As primary endpoint, the rate of patients with pathological complete remissions (pCR) will be compared exploratively between the treatment arms and to expectations derived from historical data.;Secondary Objective: • Safety of the respective combination sequences (Toxicity assessment according to NCI CTCAE V.4.0) • Surgical morbidity and complications • Pathological staging, tumor downstaging • R0 resection rate; negative circumferential resection rate • Rate of sphincter-sparing surgery • Relapse-free survival (local / distant / overall) • Overall survival • Translational / biomarker studies;Primary end point(s): The rate of patients with pathological complete remissions (pCR) will be compared exploratively between the treatment arms and to expectations derived from historical data.;Timepoint(s) of evaluation of this end point: End of therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety of the respective combination sequences (Toxicity assessment according to NCI CTCAE V.4.0) • Surgical morbidity and complications • Pathological staging, tumor downstaging • R0 resection rate; negative circumferential resection rate • Rate of sphincter-sparing surgery • Relapse-free survival (local / distant / overall) • Overall survival • Translational / biomarker studies;Timepoint(s) of evaluation of this end point: after 5 year follow up | — |
Countries
Germany
Contacts
Public ContactStudiensekretariat
University Hospital Frankfurt, Goethe University
Outcome results
None listed