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

Sponsor

Myriad Genetic Laboratories, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT01468623

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer, Metastatic	Other: Pharmacokinetic 5-FU dose adjustment using OnDose® assay Other: Standard of care	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

51 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2011

Anticipated Primary Completion Date :

Sep 1, 2016

Anticipated Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OnDose® 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 OnDose is a commercially available assay to measure concentration of 5-FU exposure. Other Names: OnDose®
Active Comparator: Body Surface Area (BSA) 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 Patients' dose of 5-FU will be based on Body Surface Area (BSA).

Arm

Intervention/Treatment

Experimental: OnDose®

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

OnDose is a commercially available assay to measure concentration of 5-FU exposure.

Other Names:

OnDose®

Active Comparator: Body Surface Area (BSA)

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

Patients' dose of 5-FU will be based on Body Surface Area (BSA).

Outcome Measures

Primary Outcome Measures

Overall response rate (ORR) [6 months]

Secondary Outcome Measures

Progression-free survival (PFS) [30 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	City	State	Country
1	Birmingham	Alabama	United States
2	Corona	California	United States
3	Fountain Valley	California	United States
4	La Jolla	California	United States
5	Modesto	California	United States
6	Ranch Cucamonga	California	United States
7	Riverside	California	United States
8	Santa Rosa	California	United States
9	Washington	District of Columbia	United States
10	Merrit Island	Florida	United States
11	Ocala	Florida	United States
12	Titusville	Florida	United States
13	Viera	Florida	United States
14	Albany	Georgia	United States
15	Chicago	Illinois	United States
16	Crystal Lake	Illinois	United States
17	Galesburg	Illinois	United States
18	Grays Lake	Illinois	United States
19	Highland Park	Illinois	United States
20	Lake Forest	Illinois	United States
21	Libertyville	Illinois	United States
22	Niles	Illinois	United States
23	Skokie	Illinois	United States
24	Munster	Indiana	United States
25	Louisville	Kentucky	United States
26	Baton Rouge	Louisiana	United States
27	Metairie	Louisiana	United States
28	Ann Arbor	Michigan	United States
29	Detroit	Michigan	United States
30	Farmington Hill	Michigan	United States
31	Great Falls	Montana	United States
32	Las Vegas	Nevada	United States
33	Hackensack	New Jersey	United States
34	Johnson City	New York	United States
35	Greensboro	North Carolina	United States
36	Fargo	North Dakota	United States
37	Minot	North Dakota	United States
38	Canton	Ohio	United States
39	Columbus	Ohio	United States
40	Bend	Oregon	United States
41	Drexel Hill	Pennsylvania	United States
42	Philadelphia	Pennsylvania	United States
43	Crossville	Tennessee	United States
44	Huntsville	Tennessee	United States
45	Bedford	Texas	United States
46	Garland	Texas	United States
47	Grapevine	Texas	United States
48	Kerryville	Texas	United States
49	McAllen	Texas	United States
50	San Antonio	Texas	United States
51	Tyler	Texas	United States
52	Waco	Texas	United States
53	Ogden	Utah	United States
54	Salt Lake City	Utah	United States
55	Fairfax	Virginia	United States
56	Newport News	Virginia	United States
57	Edmonds	Washington	United States
58	Seattle	Washington	United States