Phase II of Naltrexone in Hormone-Refractory Metastatic Breast Cancer

Phase 2

Terminated

Conditions: Breast Cancer

Interventions: Drug: naltrexone
Procedure: PET scan

Registration Number: NCT00379197

Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary: RATIONALE: Estrogen can cause the growth of breast cancer cells. Naltrexone may fight breast cancer by blocking the use of estrogen by the tumor cells. Naltrexone may also stop the growth of breast cancer by impairing blood flow to the tumor.

PURPOSE: This phase II trial is studying how well naltrexone works in treating women with metastatic breast cancer that is no longer responsive to previous hormone therapy.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 13

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Naltrexone	PET scan	Naltrexone 50 mg will be taken orally once a day every day of a 28 day treatment course (cycle 1) and continue for another identical 28 day treatment (cycle 2) . PET scan will be performed after cycle 1 and cycle 2 complete.
Naltrexone	naltrexone	Naltrexone 50 mg will be taken orally once a day every day of a 28 day treatment course (cycle 1) and continue for another identical 28 day treatment (cycle 2) . PET scan will be performed after cycle 1 and cycle 2 complete.

Primary Outcome Measures

Name	Time	Method
Disease Response	Week 4	A response is the number of participants whose tumor demonstrated a decrease in FDG uptake (SUV) by 50% or greater in at least one of the metastatic sites as measured by PET imaging at the end of 4 weeks of treatment compared to baseline.

Secondary Outcome Measures