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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by University Hospital of Crete.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University Hospital of Crete
ClinicalTrials.gov Identifier:
NCT00755118
First received: September 17, 2008
Last updated: March 13, 2012
Last verified: July 2011
  Purpose

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 Intervention Phase
Colorectal Cancer
Drug: Oxaliplatin
Drug: 5-Fluorouracil
Drug: Leucovorin
Drug: Bevacizumab
Drug: Irinotecan
Drug: Cetuximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University Hospital of Crete:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: 3 - 6 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time To Progression [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Toxicity profile [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Symptoms improvement [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Probability of 1-year survival (%) ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: October 2008
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
LoHP/AIO/Avastin->CPT-11/AIO/Erbitux
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 72 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00755118

Contacts
Contact: Dora Hatzidaki +302810392570 dorachat@med.uoc.gr
Contact: Eva Maragkoudaki +302810392857 dorachat@med.uoc.gr

Locations
Greece
University Hospital of Crete, Dep of Medical Oncology Recruiting
Heraklion, Crete, Greece
Contact: Dora Hatzidaki    +302810392570    dorachat@med.uoc.gr   
Contact: Eva Maragkoudaki    +302810392857    dorachat@med.uoc.gr   
Principal Investigator: Nikos Vardakis, MD         
University General Hospital of Alexandroupolis, Dep of Medical Oncology Recruiting
Alexandroupolis, Greece
Contact: Dora Hatzidaki    +302810392570    dorachat@med.uoc.gr   
Contact: Eva Maragkoudaki    +302810392857    dorachat@med.uoc.gr   
"IASO" General Hospital of Athens, 1st Dep of Medical Oncology Recruiting
Athens, Greece
Contact: Dora Hatzidaki    +302810392570    dorachat@med.uoc.gr   
Contact: Eva Maragkoudaki    +302810392857    dorachat@med.uoc.gr   
Principal Investigator: Stelios Giassas, MD         
Sponsors and Collaborators
University Hospital of Crete
Investigators
Principal Investigator: Nikos Vardakis, MD University Hospital of Crete, Dep of Medical Oncology
  More Information

No publications provided

Responsible Party: N.Vardakis, University Hospital of Crete
ClinicalTrials.gov Identifier: NCT00755118     History of Changes
Other Study ID Numbers: CT/08.28
Study First Received: September 17, 2008
Last Updated: March 13, 2012
Health Authority: Greece: National Organization of Medicines

Keywords provided by University Hospital of Crete:
Metastatic colorectal cancer
Second line
Irinotecan
Cetuximab
Bevacizumab

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Irinotecan
Bevacizumab
Cetuximab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on July 20, 2014