NCT00755118

Lohp, 5-Fu/Lv and Bevacizumab, Alternative With Cpt-11, 5-Fu/Lv and Cetuximab In Metastatic Crc

Phase II Study Of Weekly Administration Oxaliplatin Plus 5-Fu/Lv (Aio Regimen) Plus Bevacizumab, Alternative With Irinotecan Plus 5-Fu/Lv(Aio Regimen) Plus Cetuximab, As Salvage Treatment In Pretreated Patients With Mcrc

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: University Hospital of Crete · Academic / Other
• Sex: All
• Age: 18 Years – 72 Years
• Healthy volunteers: Not accepted

Summary

The aim of this study is to evaluate the efficacy of the effective drugs in a alternating chemotherapy schedules in pretreated patients with mCRC, who have received all effective drugs.

Detailed description

Colorectal cancer is a major cause of death worldwide and is ranked third in incidence and deaths from cancer in the USA for men and women. Incidence and mortality have been decreasing steadily in past decades, with 5-year survival for patients diagnosed in 1996-2002, being about 65%. Although curative surgical resection is possible in 70-80% of patients at diagnosis, almost half of them will develop local or/and metastatic recurrence and will die of the disease. There are currently three active cytotoxic agents that have been shown to be effective in the treatment of advanced colorectal cancer: 5-Fluorouracil combined with Leucovorin (5-FU/LV), Irinotecan and Oxaliplatin. During the last few years, the median overall survival of patients with advanced CRC has been substantially increased from 12 months to about 21-22 months, when combination of these chemotherapeutic agents are administered. Combinations of 5-Fluorouracil/Leucovorin (5-FU/LV) either as bolus (Roswell Park) or infusional administration (De Gramont schedule) r weekly infusional (AIO regimen), combined with Irinotecan or Oxaliplatin accepted as the mainstay of first line treatment. The advent of targeted therapy further expanded treatment options for patients with mCRC.In particular, inhibition of Epidermal Growth Factor Receptor (EGFR) and angiogenesis by blocking Vascular Endothelial Growth Factor (VEGF) using monoclonal antibodies, led to further improvement in the outcome of patients with mCRC. EGFR is expressed by most CRCs. Cetuximab (Erbitux) is a chimeric monoclonal antibody that specifically targets EGFR. In combination with Irinotecan, Cetuximab is approved for the treatment of EGFR-expressing mCRC, that has failed prior Irinotecan-based therapy, suggesting that Cetuximab may circumvent Irinotecan resistance. Bevacizumab (Avastin) is a monoclonal antibody against Vascular Endothelial Growth Factor (VEGF). In CRC, increased VEGF expression correlates with invasiveness, vascular density, metastasis, recurrence and prognosis. In a phase 2 trial of treatment of CRC, the addition of bevacizumab to FU/LV increased the response rate, the median time to disease progression, and the median duration of survival. Recently, it has been shown in randomized phase 2 trials that bevacizumab, when combined with irinotecan plus bolus FU/LV in the first line treatment of metastatic CRC, and with oxaliplatin plus continuous FU/LV (FOLFOX) in second-line treatment leads to an increased median survival, progression-free survival (PFS), and response rate compared with cytotoxic chemotherapy alone.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Oxaliplatin	Oxaliplatin (I.V) 85mg/m2 on week 1 and week 3 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity
DRUG	5-Fluorouracil	5-Fluorouracil (I.V) 1750mg/m2 on week 1,2,3 and 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity
DRUG	Leucovorin	Leucovorin (I.V) 500mg/m2 on week 1,2,3 and 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity
DRUG	Bevacizumab	Bevacizumab (I.V) 10mg/Kg on week 1 and week 3 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity
DRUG	Irinotecan	Irinotecan (I.V) 110mg/m2 on week 2 and week 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity
DRUG	Cetuximab	Cetuximab (I.V) 500mg/m2 on week 2 and week 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity

Timeline

• Start date: 2008-10-01
• Primary completion: 2012-08-01
• Completion: 2012-08-01
• First posted: 2008-09-18
• Last updated: 2015-10-07

Locations

3 sites across 1 country: Greece