Efficacy And Safety Of Xeliri + Avastin Followed By Xelox + Avastin Or Reverse Sequence In Metastatic Colorectal Cancer
Status:
Completed
Trial end date:
2017-08-31
Target enrollment:
Participant gender:
Summary
Since its introduction, 5-fluorouracil (5-FU) has been the cornerstone of treatment for
metastatic colorectal cancer (mCRC). Meanwhile the oral 5FU pro-drug Capecitabine (Xeloda®)
proved equivalence to 5-FU and is a well tolerated alternative combination partner for
Irinotecan (XELIRI) or Oxaliplatin (XELOX) which are widely used for first line treatment of
mCRC. Recent advances in molecular biology have resulted in the development of an inhibitor
of the vascular endothelial growth factor (VEGF) by the monoclonal humanized antibody
bevacizumab (Avastin®).
XELOX or XELIRI +bevacizumab have been investigated in several trials, but not in an approach
with clearly defined cross-wise XELIRI-XELOX change criteria. This trial investigates two
different sequential treatment options with XELIRI/ XELOX in first and second line with the
addition of bevacizumab and tries to give answer to the question if there is an optimal
sequence for the benefit of the patient.
This is a prospective, randomized, open-label, 2-arm pilot trial in patients with mCRC who
did not receive systemic treatment for their metastatic disease. The study is designed to
evaluate the efficacy of XELIRI followed by XELOX and XELOX followed by XELIRI + bevacizumab
in terms of Duration of Disease Control (DDC).
Patients will be treated with an established first line therapy consisting of either XELOX or
XELIRI + bevacizumab. The chemotherapy treatment will be given for 6 months except prior
disease progression, unacceptable toxicity or patient refusal. Bevacizumab will be given
until disease progression, unacceptable toxicity or patient refusal.
Capecitabine can be given in addition at the investigators' discretion until disease
progression, unacceptable toxicity or patient refusal.
If serious side effects occur despite adequate dose reduction, Oxaliplatin or Irinotecan
should be discontinued. In case of Oxaliplatin or Irinotecan-related discontinuation
Capecitabine and Bevacizumab should be continued. If Capecitabine also has to be discontinued
in first line treatment bevacizumab should be continued. In case of permanent discontinuation
of bevacizumab for toxicities, chemotherapy should be continued.
Upon completion of first line chemotherapy patients with disease control will receive
bevacizumab maintenance treatment. On investigators decision patients can receive
Capecitabine as additional maintenance treatment.
The primary endpoint is to determine the efficacy of a modified XELIRI + bevacizumab followed
by XELOX + bevacizumab scheme at progression in comparison with the reverse sequence based on
DDC.
Secondary endpoints are first line progression-free survival (PFS), second line PFS, overall
response rate, time to response, duration of response, overall survival, tumor assessments
(based on RECIST criteria) using CT scans, MRI scans, X-ray, bone scan, clinical examination.