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

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