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

University Hospital of Crete

Status and phase

Terminated

Phase 2

Conditions

Colorectal Cancer

Treatments

Drug: Oxaliplatin

Drug: Irinotecan

Drug: Bevacizumab

Drug: 5-Fluorouracil

Drug: Cetuximab

Drug: Leucovorin

Study type

Interventional

Funder types

Other

Identifiers

NCT00755118

CT/08.28

Details and patient eligibility

About

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.

Full 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.

Enrollment

24 patients

Sex

All

Ages

18 to 72 years old

Volunteers

No Healthy Volunteers

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