Oxaliplatin Microdosing Assay in Predicting Exposure and Sensitivity to Oxaliplatin-Based Chemotherapy

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of [14C] (carbon C 14) oxaliplatin microdose as a clinical
assay to predict oxaliplatin exposure.

SECONDARY OBJECTIVES:

I. To estimate the degree to which a [14C]oxaliplatin microdose predicts the observed
pharmacokinetics of standard dose oxaliplatin.

II. To validate that intrapatient variation of exposure to a [14C]oxaliplatin microdose is
less than 5%.

III. To detect the levels of oxaliplatin-deoxyribonucleic acid (DNA) adducts induced by
oxaliplatin microdosing in peripheral blood mononuclear cells (PBMCs), and correlate the
results with patient response and progression free survival on oxaliplatin-based
chemotherapy.

IV. To develop preliminary safety data of [14C]oxaliplatin microdosing for future studies.

OUTLINE:

Patients receive carbon C 14 oxaliplatin microdose intravenously (IV) over 120 minutes.
Beginning not more than 4 weeks after the initial carbon C 14 oxaliplatin microdose
administration, patients receive FOLFOX comprised of leucovorin calcium IV, fluorouracil IV
over 2 hours (over 46-48 hours via ambulatory infusion pump on days 1 and 2), and oxaliplatin
(contain carbon C 14 microdose course I only) IV over 2 hours on day 1. Courses repeat every
14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

- Histologically or cytologically confirmed locally advanced or metastatic colon or
rectal adenocarcinoma

- Intent to treat the patient with a leucovorin calcium, fluorouracil, and oxaliplatin
(FOLFOX) chemotherapy regimen containing fluorouracil (5-FU), leucovorin, and
oxaliplatin according to clinical standard practice; the intent should be to dose
oxaliplatin at 85 mg/m^2 on an every 2 week basis

- Treatment with any additional Food and Drug Administration (FDA)-approved biologic
agent (i.e. bevacizumab, cetuximab, or panitumumab) is allowed according to standard
practice

- Prior radiation or surgery is allowed, but should be finished at least 2 weeks prior
to study enrollment; if a participant has prior radiation therapy, at least one
measurable lesion outside of the radiation field should be available for the
evaluation of response to chemotherapy

- Any number of prior therapies other than oxaliplatin is allowed

- Zubrod performance status equal to or less than 2 (Karnofsky equal to or greater than
50%)

- Life expectancy of at least 3 months

- Absolute neutrophil count greater than or equal to 1,500/microL

- Platelets greater than or equal to 100,000/microL

- Total bilirubin less than 3 x institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase) less than
or equal to 5 x ULN

- Creatinine less than 1.5 x ULN

- Women of child bearing potential must not be pregnant; a pre-study pregnancy test must
be negative

- Women of child-bearing potential must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for 30 days
after study participation

- Men must agree to use adequate contraception (barrier method or abstinence) prior to
study entry and for 30 days after study participation

- Ability to understand and willing to sign a written informed consent document

Exclusion Criteria:

- Prior treatment with oxaliplatin

- Patients must not receive concomitant radiation

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Participants who are pregnant or nursing

- Participants who are allergic to any platinum agent

- Participants who have more than grade 1 peripheral neuropathy