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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00755118
• Other study ID #: CT/08.28
• Status: Terminated
• Phase: Phase 2
• First received: September 17, 2008
• Last updated: October 6, 2015
• Start date: October 2008
• Est. completion date: August 2012

Study information

• Verified date: October 2015
• Source: University Hospital of Crete
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: National Organization of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 72 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

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
• 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
• 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
• 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
• 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
• 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

Locations

Country	Name	City	State
Greece	University General Hospital of Alexandroupolis, Dep of Medical Oncology	Alexandroupolis
Greece	"IASO" General Hospital of Athens, 1st Dep of Medical Oncology	Athens
Greece	University Hospital of Crete, Dep of Medical Oncology	Heraklion	Crete

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital of Crete

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate		3 - 6 month	No
Secondary	Time To Progression		1 year	No
Secondary	Toxicity profile		28 days	Yes
Secondary	Quality of life		28 days	No
Secondary	Symptoms improvement		28 days	No
Secondary	Overall Survival		Probability of 1-year survival (%)	No