Patient case: 61-year-old male with Ampullary carcinoma. Genetic variant: KRAS. Other conditions: None.

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

Summary: The objective of this trial is to obtain evidence that, in patients with RAS wildtype tumors, a chemotherapy-free combined modality treatment with panitumumab is clearly superior to radiotherapy alone and achieves a pCR rate comparable to that after radiochemotherapy including two-drug combinations while reducing the toxicity compared to these two-drug regimens.


Eligibility: 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

Relevance to patient case: not relevant