Study Comparing Optimized 5-FU Dosing and Standard Dosing in Metastatic Colorectal Cancer Patients Treated With mFOLFOX6

Study Overview
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Brief Summary
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The purpose of this study is to compare OnDose® based pharmacokinetic administration of 5-FU versus standard Body Surface Area (BSA) based administration of 5-FU in patients with metastatic colorectal cancer treated with mFOLFOX6, with or without bevacizumab, to determine if the use of OnDose® achieves an improvement in the Overall Response Rate (ORR) relative to BSA dosing response.

Official Title
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A Prospective, Randomized, Open-label Trial Comparing OnDose® AUC Optimized 5-FU Based Administration Versus Standard Body Surface Area (BSA) Dosing in Metastatic Colorectal Cancer Patients (mCRC) Treated With mFOLFOX6

Conditions
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Colorectal Cancer, Metastatic

Intervention / Treatment
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* Other: Pharmacokinetic 5-FU dose adjustment using OnDose® assay
* Other: Standard of care


Participation Criteria
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Eligibility Criteria
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Selection Criteria: Patients with histologically confirmed metastatic colorectal cancer No prior chemotherapy for the treatment of metastatic colorectal cancer At least one measurable lesion by CT or MRI of ≥ 20 mm (if conventional CT scan) or ≥ 10 mm (if spiral CT scan) ECOG Performance Status (ECOG-PS) status ≤ 2 At least 18 years of age Life expectancy > 6 months Must be able and willing to give written informed consent Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial. Nursing patients are excluded. Sexually active men must also use acceptable contraceptive methods (abstinence, condom). ANC count greater than or equal to 1,500/ mm³ Platelets greater than or equal to 100,000/ mm³ Serum creatinine less than or equal to 2x upper limit of normal (normal range (male): 97-137 mL/min; (female): 88-128 mL/min) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3x the upper limit of normal (≤ 5.0 x ULN is acceptable if liver has tumor involvement) (ALT normal range: < 41 iu/L (male), < 31 iu/L (female); AST normal range: < 37 iu/L (male), < 31 iu/L (female)). Prothrombin Time (PT), activated partial thromboplastin time (aPTT) and INR ≤ 1.5 x ULN (INR normal range: 0.8-1.2) or in the therapeutic range if on anticoagulation. Hemoglobin greater than or equal to 9 gm/dl (may be corrected by transfusion prior to 5-FU treatment with investigator approval).

Ages Eligible for Study
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Minimum Age: 18 Years

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OnDose®<br>Patients will receive FOLFOX6 with or without bevacizumab (Avastin). Patients' 5-FU dose will be optimized by measuring the Area Under the Curve (AUC) of 5-FU by the commercially available OnDose® assay and their dose for subsequent cycles adjusted following a pre-established dose adjustment algorithm. | Other: Pharmacokinetic 5-FU dose adjustment using OnDose® assay<br>* OnDose is a commercially available assay to measure concentration of 5-FU exposure.<br>* Other names: OnDose®;|
| Active Comparator: Body Surface Area (BSA)<br>Patients will receive FOLFOX6 with or without bevacizumab (Avastin). Patients will receive 5-FU based on traditional BSA calculation and their dose adjusted based on standard clinical practice. OnDose® AUC measurements will be performed for this arm but will not be used for dose adjustment. | Other: Standard of care<br>* Patients' dose of 5-FU will be based on Body Surface Area (BSA).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, metastatic, FOLFOX6, 5-FU, First line, bevacizumab