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

• Status: Unknown status
• Trial end date: 2016-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: WiSP Wissenschaftlicher Service Pharma GmbH
• Collaborators: Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH; Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
• Treatments: Antibodies, Monoclonal; Panitumumab

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