Phase II of Naltrexone in Hormone-Refractory Metastatic Breast Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Study of Naltrexone for the Treatment of Hormone-Refractory, Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: naltrexone
* Procedure: PET scan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naltrexone<br>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. | Drug: naltrexone<br>* Naltrexone 50 mg will be orally taken once daily for 28 day (cycle 1), and continues once daily for another 28 days (cycle 2) without interval.<br>* Other names: REVIA;Procedure: PET scan<br>* Patients will receive PET scan approximately one hour after being injected with 2-Deoxy-2-[18F]fluoro-D-Glucose (FDG). PET scans will be performed after the completion of cycle 1 and cycle 2 and during the 1 year follow-up.<br>* Other names: Positron-emission tomography scan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Response | 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. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Event | First time when maximum SUV is higher than that at baseline within 1 year of study entry. | From Baseline to 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, estrogen receptor positive, recurrent breast cancer, hormone-refractory, metastatic breast cancer