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

Myriad Genetic Laboratories

Status and phase: Terminated; Phase 4

Conditions: Colorectal Cancer, Metastatic

Treatments: Other: Standard of care; Other: Pharmacokinetic 5-FU dose adjustment using OnDose® assay

Study type: Interventional

Funder types: Industry

Identifiers

NCT01468623

PROFUSE-2011

Details and patient eligibility

About

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.

Enrollment: 51 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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51 participants in 2 patient groups

OnDose®

Experimental group

Description:

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.

Treatment:

Other: Pharmacokinetic 5-FU dose adjustment using OnDose® assay

Body Surface Area (BSA)

Active Comparator group

Description:

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.

Treatment:

Other: Standard of care