Neoadjuvant Radiochemotherapy Combined With Panitumumab in Locally Advanced KRAS Wild-type Rectal Cancer (NEOREC-1)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Neoadjuvant Radiochemotherapy Combined With Panitumumab in Locally Advanced KRAS Wild-type Rectal Cancer|
- Histopathological complete response rate (pCR) [ Time Frame: at week 14 after tumor resection ] [ Designated as safety issue: No ]pCR determined by means of the resection specimens
- Objective tumor response rate assessed by MRI of the pelvis (incl. RECIST) [ Time Frame: at day 14 and week 12 ] [ Designated as safety issue: No ]
- Metabolic tumor response rate assessed by means of changes in the standardized uptake values (SUV) using FDG-PET-CT (incl. RECIST) [ Time Frame: day 14 and at week 14 before surgery ] [ Designated as safety issue: No ]
- Pathological tumor regression grades will be classified according to Becker [ Time Frame: at week 14 after surgery ] [ Designated as safety issue: No ]
- Quality of Life (QoL) will be assessed using the EORTC QLQ-C30 in combination with the colorectal cancer-specific quality of life questionaire module (QLQ-CR29) [ Time Frame: between day 0 and week 18 end of study ] [ Designated as safety issue: No ]
- distant metastases-free survival [ Time Frame: during follow up every 6 months until death or until 2 years after LPO ] [ Designated as safety issue: No ]distant metastases-free survival after EOS
- relapse-free survival [ Time Frame: during follow up every 6 months until death or until 2 years after LPO ] [ Designated as safety issue: No ]relapse-free survival after end of study
- overall survival [ Time Frame: during follow up every 6 months until death or until 2 years after LPO ] [ Designated as safety issue: No ]overall survival after EOS
|Study Start Date:||July 2011|
|Study Completion Date:||September 2013|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01443377
|National Center for Tumor Disease (NCT)|
|Heidelberg, BW, Germany, 69120|
|Krankenhaus Nord West, Radioonkologische Klinik|
|Frankfurt, Hessen, Germany, 60488|
|Principal Investigator:||Dirk Jaeger, Prof. Dr||National Center of Tumor Disease, Heidelberg|