Randomized Phase III Study of Folfiri+Avastin Versus Xeliri+Avastin as 1st Line Treatment of CRC
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ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2039690 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:This phase II study will evaluate the efficacy of the combination of two monoclonal antibodies (Avastin + Erbitux) with irinotecan, in patients with colorectal cancer progressed after 1st line treatment with FOLFIRI Avastin or XELIRI Avastin.
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2012-09-30 | E-MEXP-3296 | biostudies-arrayexpress
Project description:The purpose of this randomised phase III trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3methyglutaryl coenzyme A reductase inhibitor, to XELIRI/FOLFIRI chemotherapy regimens confers a clinical benefit to patients with previously treated metastatic colorectal cancer.We undertook a double-blind, placebo-controlled phase III trial of 269 patients previously treated for metastatic colorectal cancer and enrolled in 5 centres in South Korea. Patients were randomly assigned (1:1) to one of the following groups: FOLFIRI/XELIRI plus simvastatin (40?mg) or FOLFIRI/XELIRI plus placebo. The FOLFIRI regimen consisted of irinotecan at 180?mg?m(-2) as a 90-min infusion, leucovorin at 200?mg?m(-2) as a 2-h infusion, and a bolus injection of 5-FU 400?mg?m(-2) followed by a 46-h continuous infusion of 5-FU at 2400?mg?m(-2). The XELIRI regimen consisted of irinotecan at 250?mg?m(-2) as a 90-min infusion with capecitabine 1000?mg?m(-2) twice daily for 14 days. The primary end point was progression-free survival (PFS). Secondary end points included response rate, duration of response, overall survival (OS), time to progression, and toxicity.Between April 2010 and July 2013, 269 patients were enrolled and assigned to treatment groups (134 simvastatin, 135 placebo). The median PFS was 5.9 months (95% CI, 4.5-7.3) in the XELIRI/FOLFIRI plus simvastatin group and 7.0 months (95% CI, 5.4-8.6) in the XELIRI/FOLFIRI plus placebo group (P=0.937). No significant difference was observed between the two groups with respect to OS (median, 15.9 months (simvastatin) vs 19.9 months (placebo), P=0.826). Grade?3 nausea and anorexia were noted slightly more often in patients in the simvastatin arm compared with with the placebo arm (4.5% vs 0.7%, 3.0% vs 0%, respectively).The addition of 40?mg simvastatin to the XELIRI/FOLFIRI regimens did not improve PFS in patients with previously treated metastatic colorectal cancer nor did it increase toxicity.
| S-EPMC4815882 | biostudies-literature
Project description:The aim of this study was to compare the efficacy, safety and survival rate of a treatment regimen comprising capecitabine plus irinotecan (XELIRI) to those of a standard regimen comprising leucovorin, fluorouracil and irinotecan (FOLFIRI), to determine the correlation among the inherited genetic variations in UGT1A1, UGT1A7 and UGT1A9. A total of 84 consecutive patients with histologically confirmed metastatic colorectal cancer (mCRC) were included in the study. All patients were treated with FOLFIRI or XELIRI. The median progression-free survival time was 4.4 months for FOLFIRI and 5.7 months for XELIRI (hazard ratio=1.35; 95% confidence interval, 0.83-2.21; P=0.22). When compared with FOLFIRI (6.34%), XELIRI was associated with lower rates of severe toxicity (3.29) (P=0.026) and similar disease control rates (69.57% for FOLFIRI and 61.11% for XELIRI; P=0.49). In total, 17 single nucleotide polymorphisms were identified, five of which revealed an association with grade 3/4 neutropenia, including UGT1A7*4; however, UGT1A1*28 and UGT1A1*6, which have been previously reported, were not significant. Additionally, H2 haplotypes, which include UGT1A9*22, and H5 and H7 haplotypes, which include UGT1A7*2, UGT1A7*3 and UGT1A7*4, were associated with a higher risk of severe neutropenia. In conclusion, XELIRI is an effective treatment regimen with acceptable response rates and tolerability for mCRC patients as a second-line treatment. Furthermore, inherited genetic variations in UGT1A1, UGT1A7 and UGT1A9 are associated with grade 3/4 neutropenia.
| S-EPMC4156196 | biostudies-literature
Project description: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.
| 2165111 | ecrin-mdr-crc
Project description:The primary purpose of this study is to determine the non-inferiority of overall survival XELIRI with or without Bevacizumab compared with FOLFIRI with or without Bevacizumab as Second-line therapy in Patient with Metastatic Colorectal Cancer.
| 2155723 | ecrin-mdr-crc
Project description:Capecitabine and irinotecan combination therapy (XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer (mCRC). Recently, in the Association of Medical Oncology of the German Cancer Society (AIO) 0604 trial, tri-weekly XELIRI plus bevacizumab, with reduced doses of irinotecan (200 mg/m2 on day 1) and capecitabine (1600 mg/m2 on days 1-14), repeated every 3 weeks, has shown favorable tolerability and efficacy which were comparable to those of capecitabine and oxaliplatin (XELOX) plus bevacizumab. The doses of capecitabine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab (BIX) as second-line chemotherapy was well tolerated and had promising efficacy in Japanese patients.The Asian XELIRI ProjecT (AXEPT) is an East Asian collaborative, open-labelled, randomized, phase III clinical trial which was designed to demonstrate the non-inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI (5-fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second-line chemotherapy for patients with mCRC. Patients with 20 years of age or older, histologically confirmed mCRC, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and disease progression or intolerance of the first-line regimen will be eligible. Patients will be randomized (1:1) to receive standard FOLFIRI with or without bevacizumab (5 mg/kg on day 1), repeated every 2 weeks (FOLIRI arm) or XELIRI with or without bevacizumab (7.5 mg/kg on day 1), repeated every 3 weeks (XELIRI arm). A total of 464 events were estimated as necessary to show non-inferiority with a power of 80% at a one-sided ? of 0.025, requiring a target sample size of 600 patients. The 95% confidence interval (CI) upper limit of the hazard ratio was pre-specified as less than 1.3.The Asian XELIRI ProjecT is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second-line treatment option of mCRC. Trial registration ClinicalTrials.gov NCT01996306. UMIN000012263.
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Project description:This open-label single arm study will evaluate the efficacy and safety of Avastin added to XELOX or FOLFOX in patients with metastatic colorectal cancer and disease progression on 1st line therapy with FOLFIRI plus Avastin. Patients will receive either Avastin (7.5mg/kg iv infusion every 3 weeks) and standard XELOX (Xeloda [capecitabine] plus oxaliplatin) chemotherapy or Avastin (5 mg/kg iv infusion every 2 weeks) and standard FOLFOX (5-FU and leucovorin plus oxaliplatin) chemotherapy. The anticipated time on study treatment is until disease progression, and the target sample size is 100 individuals.
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Project description:Microarrays were used to determine the efficacy of bevacizumab (a monoclonal antibody against the vascular endothelial growth factor and its receptors.) on endometrial cancer cells. Endometrial cancer is the most frequent gynecologic cancer in women. Long term outcomes for patients with advanced stage or recurrent disease are poor. Targeted molecular therapy against the vascular endothelial growth factor (VEGF) and its receptors constitute a new therapeutic option for these patients. The goal of our work was to assess the potential effectiveness of inhibition of VEGF/VEGFR signaling in a xenograft model of endometrial cancer using bevacizumab (Avastin, a humanized antibody against VEGFA). We also aimed to identify molecular markers of sensitivity or resistance to this agent. We show that bevacizumab retards tumor growth in athymic mice by inhibiting molecular components of signaling pathways that sustain cell survival and proliferation. We also demonstrate that resistance to bevacizumab may involve up-regulation of antiapoptotic genes and certain proto-oncogenes.
2009-09-22 | GSE18195 | GEO