panitumumab in combination with radiotherapy in patients with locally advanced ras wildtype rectal cancer (clinical stages ii and iii)

Conditions: Rectal Cancer

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 criteria:
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

Keywords: ras-wildtype radiotherapy neoadjuvant treatment