Circulating Regulatory Lymphocytes and Outcome of Metastatic Colorectal Cancer Patients

Study Overview
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Brief Summary
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Aim of the present study is to investigate whether baseline or early post-treatment (one month after treatment commencement) frequency of peripheral T regulatory lymphocytes (Tregs OR CD4+/CD25high/FOXP3+ T cells), known to suppress antitumor immune response, may influence long-term clinical outcome (i.e. radiological response, progression-free survival or overall survival) in metastatic colorectal cancer patients treated with a standard first-line chemotherapy including fluorouracil, irinotecan and bevacizumab

Official Title
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Observational Study of the Impact of Circulating T Regulatory Cells (Tregs) on Clinical Outcome of Metastatic Colorectal Cancer (MCRC) Patients Treated With Standard Fluorouracil/Irinotecan/Bevacizumab First Line Therapy

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: fluorouracil/irinotecan/levo-folinic acid/bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with histologically or cytologically confirmed diagnosis of metastatic colorectal cancer not amenable to surgery Adjuvant treatment ended ≥6 months before the study entry No prior exposure to irinotecan and/or bevacizumab in the adjuvant treatment No prior exposure to cytotoxic drugs for the metastatic disease At least one measurable lesion according to the RECIST criteria adequate laboratory parameters (Hemoglobin level ≥ 9.0 g/dL; Neutrophil count > 1.5 x 109/L; Platelets count >100 x 109/L; Total bilirubin <1.5 time the upper-normal limits (UNL) and ASAT (SGOT) and/or ALAT (SGPT) <2.5 x UNL, or <5 x UNL in case of liver metastases; alkaline phosphatase <2.5 x UNL, or <5 x UNL in case of liver metastases; PT-INR/PTT < 1.5 x UNL;Creatinine clearance > 50 mL/min or serum creatinine <1.5 x UNL; Urine dipstick of proteinuria < 2+) Written informed consent. Patients must be accessible for treatment and follow up. Exclusion Criteria: Untreated brain metastases or spinal cord compression History of inflammatory bowel disease and/or acute or subacute bowel occlusion. Serious, non-healing wound, ulcer, or bone fracture Evidence of bleeding diathesis or coagulopathy. Uncontrolled hypertension. Clinically significant cardiovascular disease(cerebrovascular accidents ≤ 6 months, myocardial infarction ≤ 6 months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication) Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes. Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration. Treatment with any investigational drug within 30 days prior to enrolment. Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline Substance abuse, medical, psychological or social conditions that may interfere with the participation into the study or the evaluation of study results Patients unable to swallow oral medications
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fluorouracil/irinotecan/levo-folinic acid/bevacizumab|standard first line chemotherapy with: bevacizumab 5 mg/kg intravenous (i.v.) infusion on day 1; irinotecan 180 mg/m2 i.v. infusion on day 1, levo-folinic acid 200 mg/m2 i.v. infusion on day 1, 5-fluorouracil 400 mg/m2 i.v. bolus on day 1 and 2,400 mg/m2 i.v. infusion over 46 hours; infusions repeated every 2 weeks|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of Tregs frequency on overall survival |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of Tregs frequency progression free survival |  | 12 months | 
| Impact of Tregs frequency radiologic response rate |  | 6 months |