Oxaliplatin in Treating Patients With Metastatic Breast Cancer

PRIMARY OBJECTIVES:

I. To detect the levels of oxaliplatin-deoxyribonucleic acid (DNA) adducts induced by
oxaliplatin microdosing in tumor tissue and peripheral blood mononuclear cells (PBMC), and
correlate the results with patient response to oxaliplatin-based chemotherapy.

SECONDARY OBJECTIVES:

I. Evaluate the efficacy of single agent oxaliplatin treatment (130mg/m^2, 2 hr intravenously
[IV] day 1; every 3 weeks) in pre-treated, metastatic breast cancer patients.

II. Evaluate the toxicity of oxaliplatin microdose and chemotherapy treatment in this patient
population.

III. Determine the pharmacokinetic (PK) parameters of oxaliplatin microdosing and correlate
with the PK parameters of therapeutic oxaliplatin.

IV. Determine whether the pharmacokinetics of oxaliplatin microdosing affects
oxaliplatin-induced DNA damage and, therefore, patient response to chemotherapy.

V. Detect repair of DNA adducts in PBMC and correlate with patient response to
oxaliplatin-based chemotherapy.

VI. Correlate the adduct and patient response data to DNA repair genes, such as excision
repair cross-complementing (ERCC)1 levels as measured by reverse transcriptase-polymerase
chain reaction (RT-PCR).

OUTLINE:

PHASE 0: Patients receive carbon C 14 oxaliplatin IV over 2 minutes on day 1.

PHASE II: Patients receive oxaliplatin IV over 2 hours on day 1. Courses repeat every 3 weeks
in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 6 months.

Inclusion Criteria:

- Participants must have metastatic breast cancer that can be biopsied or resected
around 48 hours after dosing with one microdose of [14C]oxaliplatin (carbon C 14
oxaliplatin)

- 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

- Patients with metastatic breast cancer for which no standard therapy exists will be
recruited for this study; more specifically, for patients with hormone receptor
positive/human epidermal growth factor receptor 2 (Her2) negative disease, this
includes previous therapy with tamoxifen or an aromatase inhibitor and one line of
chemotherapy in the metastatic setting; for patients with Her2 positive disease, this
includes 2 lines of Her2 directed therapy in the metastatic setting; and for patients
with triple negative disease, this includes one line of chemotherapy in the metastatic
setting; once we have identified the dose of [14C]oxaliplatin, we will only recruit
triple negative breast cancer patients that progressed after one line of chemotherapy
in the metastatic setting

- Any number of prior therapies other than oxaliplatin is allowed

- Eastern Cooperative Oncology Group (ECOG) 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 1.5 X institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) less
than or equal to 2.5 X ULN

- Creatinine less than 1.5 X ULN

- No pre-existing sensory neuropathy > grade 1

- 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:

- Patients must not receive concomitant radiation with chemotherapy if they do not have
any measurable lesions outside of the radiation field

- 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 platinum agent

- Participants who have more than grade 1 peripheral neuropathy