A Open Label, Non Randomized, Phase Two Trial in Metastatic Colorectal Cancer (mCRC) With the Combination of m FOLFIRI Plus Aflibercept as First Line Treatment: MINOAS Trial

Hellenic Oncology Research Group10 sites in 1 country31 target enrollmentJanuary 2016

ConditionsMetastatic Colorectal Cancer

Interventions5 Fluorouracil Leucovorin Irinotecan Aflibercept

Drugs5 Fluorouracil Leucovorin Irinotecan Aflibercept

Overview

Phase: Phase 2
Intervention: 5 Fluorouracil
Conditions: Metastatic Colorectal Cancer
Sponsor: Hellenic Oncology Research Group
Enrollment: 31
Locations: 10
Primary Endpoint: Overall Response Rate
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Investigators propose to study the combination of m FOLFIRI plus Aflibercept in a Phase II trial of patients with metastatic colorectal cancer. The promising results of aflibercept derived from preclinical studies and from clinical trials conducted in patients with refractory of recurrent to oxaliplatin-based 1st line treatment in patients with mCRC open the field to explore such therapeutic approaches in the 1st line setting in combination with the FOLFIRI regimen.

Detailed Description

Colorectal cancer accounts for 8% of all malignant tumors in adults and is considered as a major cause of cancer morbidity and mortality worldwide. 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 with the liver been the most common site of metastatic spread from CRC. Combinations of infusional administrated 5-fluorouracil/Leucovorin with irinotecan or oxaliplatin are accepted as the mainstay of first-line treatment and have increase the median overall survival of patients with advanced CRC from 12 months to about 21-22 months. In addition, resection for colorectal metastases (mainly in the liver), has become the standard of care, for patients with limited metastatic disease confounded to the liver and currently remains the only potentially curative therapy Aflibercept, also known as vascular endothelial growth factor (VEGF) Trap, is an angiogenesis inhibitor with a unique mechanism of action. Aflibercept is a recombinant fusion protein that consists of portions of human VEGFR1 and VEGFR2 extracellular domains fused to the Fc portion of human immunoglobulin G1. This fusion protein binds all forms of Vascular Endothelial Growth Factor-A, as well as VEGF-B and placental growth factor, additional angiogenic growth factors that appear to play a role in tumor angiogenesis and inflammation. Aflibercept has been shown to bind VEGF-A, VEGF-B, and placental growth factor (PlGF) with higher affinity than their native receptors. In vitro and in vivo studies have shown that aflibercept can inhibit new vessel growth and tumor vascularization in tumor models.

Registry

clinicaltrials.gov

Start Date

January 2016

End Date

March 2019

Last Updated

7 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Hellenic Oncology Research Group

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients with histologically documented adenocarcinomas of colon or rectum with unresectable metastatic disease.
•No prior treatment for metastatic disease
•Metastatic liver disease assessable with diffusion-weighted Magnetic Resonance Imaging (MRI)
•No previous treatment with bevacizumab or Cetuximab or Panitumumab.
•Patients may have receive fluoropyrimidines with or without oxaliplatin as adjuvant treatment, if they have progressed \> 12 months after the end of the last cycle of the adjuvant treatment
•Performance Status (ECOG) 0-2
•Life expectancy ≥ 3 months.
•Effective contraception for both male and female subjects if the risk of conception exists.
•Adequate laboratory parameters: Absolute neutrophils count ≥ 1.5 x 109 /L, Platelets ≥ 100 x 109 /L, Leucocytes \> 3,000/mm; Hemoglobin\> 10.5g/dl, creatinine clearance ≥ 60 ml/min, Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour, Magnesium ≥ lower limit of normal, Calcium ≥ lower limit of normal, total Bilirubin ≤ 1.5 times the upper limit of normal; aspartate and alanine aminotransferase ≤ 3 times of the upper normal limit in absence of liver metastases, or ≤5x Upper Normal Limits (UNL) in presence of liver metastases, alkaline phosphatases \< 5x UNL
•All patients will have to sign written informed consent in order to participate in the study.

Exclusion Criteria

•Known hypersensitivity reaction to the component of the treatment.
•Inability to underwent a diffusion-weighted MR Imaging at baseline and in predefined time points
•Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
•History or evidence upon physical examination of Central Nervous System (CNS) metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),
•Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
•Treatment with any other investigational medicinal product within 28 days prior to study entry.
•Other serious and uncontrolled non-malignant disease
•Uncontrolled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy.
•Gilbert's syndrome
•Intolerance to atropine sulfate or loperamide