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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00755118
Recruitment Status : Terminated (Due to poor Accrual)
First Posted : September 18, 2008
Last Update Posted : October 7, 2015
Information provided by (Responsible Party):
Vassilis Georgoulias, MD, University Hospital of Crete

Brief 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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: Oxaliplatin Drug: 5-Fluorouracil Drug: Leucovorin Drug: Bevacizumab Drug: Irinotecan Drug: Cetuximab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : October 2008
Actual Primary Completion Date : August 2012
Actual Study Completion Date : August 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1
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
Other Names:
  • Eloxatin
  • LoHP

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
Other Name: 5-FU

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
Other Name: LV

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
Other Name: Avastin

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
Other Names:
  • CPT-11
  • Campto

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
Other Name: Erbitux

Primary Outcome Measures :
  1. Objective Response Rate [ Time Frame: 3 - 6 month ]

Secondary Outcome Measures :
  1. Time To Progression [ Time Frame: 1 year ]
  2. Toxicity profile [ Time Frame: 28 days ]
  3. Quality of life [ Time Frame: 28 days ]
  4. Symptoms improvement [ Time Frame: 28 days ]
  5. Overall Survival [ Time Frame: Probability of 1-year survival (%) ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 72 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 cancer
  • Psychiatric illness or social situation that would preclude study compliance

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00755118

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University Hospital of Crete, Dep of Medical Oncology
Heraklion, Crete, Greece
University General Hospital of Alexandroupolis, Dep of Medical Oncology
Alexandroupolis, Greece
"IASO" General Hospital of Athens, 1st Dep of Medical Oncology
Athens, Greece
Sponsors and Collaborators
University Hospital of Crete
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Principal Investigator: Nikos Vardakis, MD University Hospital of Crete, Dep of Medical Oncology
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Responsible Party: Vassilis Georgoulias, MD, MD, University Hospital of Crete Identifier: NCT00755118    
Other Study ID Numbers: CT/08.28
First Posted: September 18, 2008    Key Record Dates
Last Update Posted: October 7, 2015
Last Verified: October 2015
Keywords provided by Vassilis Georgoulias, MD, University Hospital of Crete:
Metastatic colorectal cancer
Second line
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Topoisomerase I Inhibitors