Neoadjuvant Radiochemotherapy Combined With Panitumumab in Locally Advanced KRAS Wild-type Rectal Cancer (NEOREC-1)
|ClinicalTrials.gov Identifier: NCT01443377|
Recruitment Status : Completed
First Posted : September 29, 2011
Last Update Posted : May 7, 2015
|Condition or disease||Intervention/treatment||Phase|
|Rectal Cancer||Biological: Panitumumab||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Neoadjuvant Radiochemotherapy Combined With Panitumumab in Locally Advanced KRAS Wild-type Rectal Cancer|
|Study Start Date :||July 2011|
|Actual Primary Completion Date :||September 2012|
|Actual Study Completion Date :||September 2013|
- Histopathological complete response rate (pCR) [ Time Frame: at week 14 after tumor resection ]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 ]
- 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 ]
- Pathological tumor regression grades will be classified according to Becker [ Time Frame: at week 14 after surgery ]
- 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 ]
- distant metastases-free survival [ Time Frame: during follow up every 6 months until death or until 2 years after LPO ]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 ]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 ]overall survival after EOS
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|