Phase II of Naltrexone in Hormone-Refractory Metastatic Breast Cancer

OBJECTIVES:

Primary

- Determine the efficacy of naltrexone in women with hormone-refractory, metastatic breast
cancer as measured by serial fludeoxyglucose F 18 positron emission tomography-CT scans.

Secondary

- Determine the safety of naltrexone in these patients.

- Determine the median time to event (first time when maximum specific uptake values is
higher than that at baseline) within 1 year of study entry.

OUTLINE: This is an open-label study.

Patients receive oral naltrexone once daily for 8 weeks in the absence of disease progression
or unacceptable toxicity. After 8 weeks, patients may continue naltrexone off study at the
discretion of the physician.

Patients undergo fludeoxyglucose F 18 positron emission tomography-CT scans at baseline, week
4, week 8, and periodically thereafter.

After completion of study treatment, patients are followed for up to 1 year.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Inclusion Criteria:

- Metastatic, hormone-receptor positive breast cancer

- Disease that has progressed despite previous systemic hormonal therapy. Hormone
therapy must be terminated at least 2 weeks prior to study enrollment.

- Prior chemotherapy, immunotherapy, or biological therapy is allowed if at least 3
weeks since last treatment. Patient must recover from the acute toxic effects of the
treatment prior to study enrollment.

- Measurable disease as defined by solid tumor response (RECIST) criteria or
non-measurable bone disease that is Positron-emission tomography (PET) avid

- Karnofsky performance status >70%

- Female, age 18 years or older

- Adequate organ function within 14 days of study enrollment including the following:

- Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count
(ANC) ≥ 1.5 x 10^9/L, platelets >75 x 10^9/L, and hemoglobin > 8 g/dL

- Hepatic: bilirubin ≤ 2 times the upper limit of normal (× ULN), aspartate
transaminase (AST) and alanine transaminase (ALT) ≤ 2 × ULN. (AST and ALT ≤ 5 ×
ULN is acceptable if liver has tumor involvement)

- Renal: creatinine ≤ 2 times the upper limit of normal

- Women of childbearing potential are required to use an effective method of
contraception (ie, a hormonal contraceptive, intrauterine device, diaphragm with
spermicide, condom with spermicide, or abstinence) during the study and for 3 months
after the last dose of study drug.

- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.

Exclusion criteria:

- Brain metastases unless stable for 1 month or more following radiation therapy.

- Pregnant or lactating women. PET-CT is not approved during pregnancy. A negative urine
or serum pregnancy test is required for all females of child bearing potential within
7 days prior to study entry. Pregnancy testing is not required for post-menopausal or
surgically sterilized women.

- Use of any short-acting or long-acting opioid medication (including morphine,
meperidine, oxycodone, hydromorphone, hydrocodone, fentanyl, tramadol) within 10 days
prior to study enrollment

- Pain uncontrolled with the use of non-narcotic drugs (acetaminophen or non-steroidal
medications)

- History of sensitivity to naltrexone

- Acute hepatitis or liver failure

- Immunosuppressive therapy for patients with autoimmune diseases, organ transplant, or
other indications