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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

Phase 2
18 Years
72 Years
Open (Enrolling)
Colorectal Cancer

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Trial Information

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

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.

Inclusion Criteria:

- Histologically confirmed locally advanced or metastatic colorectal cancer

- Measurable or evaluable disease according to the Response Evaluation Criteria in
Solid Tumors (RECIST)

- ECOG performance status ≤ 2

- Age 18 - 72 years

- Patients who progress after 1st line therapy with FOLFOX/AVASTIN

- Adequate liver (Bilirubin ≤ 1.5 upper normal limit, SGOT/SGPT ≤ 4 upper normal limit,
ALP ≤ 2.5 upper normal limit),renal (Creatinine ≤ 1.5 upper normal limit) and bone
marrow (ANC ≥ 1,500/mm3, PLT ≥100,000/mm3) function

- Patients must be able to understand the nature of this study

- Written informed consent

- Previous treatments with all effective drugs for metastatic colorectal cancer
(CPT-11, LOHP, 5-FU/XELODA, Erbitux, Avastin)

Exclusion Criteria:

- History of serious cardiac disease (unstable angina, congestive heart
failure,uncontrolled cardiac arrhythmias)

- History of myocardial infarction or stroke within 6 months

- Clinically significant peripheral vascular disease

- History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess
within 28 days prior to Day 0

- Major surgical procedure, open biopsy, or significant traumatic injury within 30 days
prior to Day 1

- Presence of central nervous system or brain metastases

- Evidence of bleeding diathesis or coagulopathy

- Blood pressure > 150/100 mmHg

- Pregnant or lactating woman

- Life expectancy < 3 months

- Previous radiotherapy within the last 4 weeks or > 25% of bone marrow

- Metastatic infiltration of the liver >50%

- Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction
or total colectomy

- Active infection requiring antibiotics on Day 1

- Second primary malignancy, except for non-melanoma skin cancer and in situ cervical

- Psychiatric illness or social situation that would preclude study compliance

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective Response Rate

Outcome Time Frame:

3 - 6 month

Safety Issue:


Principal Investigator

Nikos Vardakis, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospital of Crete, Dep of Medical Oncology


Greece: National Organization of Medicines

Study ID:




Start Date:

October 2008

Completion Date:

December 2012

Related Keywords:

  • Colorectal Cancer
  • Metastatic colorectal cancer
  • Second line
  • Irinotecan
  • Cetuximab
  • Bevacizumab
  • Colorectal Neoplasms