NCT01443377

Neoadjuvant Radiochemotherapy Combined With Panitumumab in Locally Advanced KRAS Wild-type Rectal Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: National Center for Tumor Diseases, Heidelberg · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study aims to investigate the combination of panitumumab and a 5-FU-based RCTX in patients with locally advanced KRAS wild-type rectal cancer.

Detailed description

Significant progress in the management of locally advanced rectal cancer has been achieved during the last decade. This includes surgical techniques as the widespread implementation of total mesorectal excision as well as preoperative radiochemotherapy (RCTX). The results of the recent randomized trials led to a current standard in which most (radio-) oncologists now use continuous-infusion 5-FU concomitantly with preoperative radiotherapy. It has been demonstrated that this provides improved tumor downstaging and local control; however, no significant differences have yet been achieved in the 5-year disease-free and overall survival rates. Thus, the challenge is to integrate more effective systemic therapy into the combined-modality programs. The combination of RCTX with novel chemotherapeutic agents like oxaliplatin and irinotecan in phase I/II trials suggested higher rates of histopathological complete remission (pCR) compared with 5-FU RCTX alone. However, due to the lack of results from randomized trials, to date no improvement of the long-term outcomes could be demonstrated, moreover, for some studies the increased pCR rate was associated with an increase in toxicity. Another strategy to improve outcome is to incorporate newer, biologically active, targeted therapies into established RCTX regimens. Because of its key role in signalling proliferation, inhibition of apoptosis and angiogenesis the epidermal growth factor receptor (EGFR) is a promising target of antitumor treatment. To date a few clinical phase I/II studies of preoperative RCTX have been initiated to evaluate EGFR inhibitors as radiosensitizer in rectal cancer. These trials demonstrated that a combination of cetuximab and RCTX could be safely applied without dose compromises of the respective treatment components. However, the pCR rates could not be improved in these studies. Given the strong preclinical rationale to combine EGFR inhibition with RCTX in rectal cancer patients, this study aims to investigate the combination of panitumumab and a 5-FU-based RCTX in patients with locally advanced KRAS wild-type rectal cancer.

Conditions

• Rectal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Panitumumab	Intravenous (IV), Panitumumab 6 mg/kg BW q2w d1-d57 (5 times total); begin on day 1 (run-in-phase) and subsequent application on days 15, 29 43 and 57.

Timeline

• Start date: 2011-07-01
• Primary completion: 2012-09-01
• Completion: 2013-09-01
• First posted: 2011-09-29
• Last updated: 2015-05-07

Locations

2 sites across 1 country: Germany