Panitumumab in Combination With Radiotherapy in Patients With Locally Advanced RAS Wildtype Rectal Cancer (Clinical Stages II and III)

Inclusion Criteria: * Histologically confirmed diagnosis of locally advanced rectal cancer (stage II or III) localised 0 - 12 cm ab ano as measured by rigid rectoscopy (i.e. lower and middle third of the rectum) * Staging requirements: trans-rectal endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) * Sufficient representative sample material for RAS analysis * Wild-type RAS (determined by an accredited local laboratory, if not available by pathology of Mannheim university) * RAS wild-type tested in * KRAS exon 2 (codons 12/13) * KRAS exon 3 (codons 59/61) * KRAS exon 4 (codons 117/146) * NRAS exon 2 (codons 12/13) * NRAS exon 3 (codons 59/61) * NRAS exon 4 (codons 117/146) * Informed consent of the patient * Aged at least 18 years * WHO Performance Status 0-2 * Life expectancy of al least 12 weeks * Adequate haematological, hepatic, renal and metabolic function parameters: * Leukocytes \> 3000/mm³ * ANC ≥ 1500/mm³ * Platelets ≥ 100,000/mm³ * Hb \> 9 g/dl * Creatinine clearance ≥ 50 ml/min and serum creatinine ≤ 1.5 x upper limit of normal * Bilirubin ≤ 1.5 x upper limit of normal * GOT-GPT ≤ 2.5 x upper limit of normal * AP ≤ 5 x upper limit of normal * Magnesium ≥ lower limit of normal * Calcium ≥ lower limit of normal Exclusion Criteria: * Lower border of the tumor localised more than 12 cm ab ano as measured by rigid rectoscopy * Distant metastases (to be excluded by CT scan of the thorax and abdomen) * cT4 tumor (as determined by MRI and/or endorectal ultrasound) * Risk of tumor involvement of the circumferential resection margin, according to the MRI assessment * Sphincter sparing is the major reason for choosing the neoadjuvant treatment approach * 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) * Serious concurrent diseases * On-treatment participation in a clinical study in the period 30 days prior to inclusion * Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment * History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan * History of HIV infection * Prior or concurrent malignancy (≤ 5 years prior to enrolment in study) except non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1 if the patient is continuously disease-free * Known allergic reactions on study medication