Naltrexone RCT for Treatment-Emergent Fatigue in Patients Receiving Radiation Therapy for Breast Cancer
Condition: Invasive Breast Cancer (Stage I-III); Ductal Carcinoma in Situ; Lobular Carcinoma in Situ; Lobular Carcinoma; Fatigue Related to Cancer Treatment
MeSH terms: Carcinoma; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Breast Carcinoma In Situ; Fatigue
Intervention: Naltrexone; Sugar Pill
Intervention MeSH terms: Naltrexone
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Invasive Breast Cancer (Stage I-III); Ductal Carcinoma in Situ; Lobular Carcinoma in Situ; Lobular Carcinoma; Fatigue Related to Cancer Treatment

Summary:

      Naltrexone is a drug which blocks some effects of chemicals called beta-endorphins that are
      made in the body. Beta-endorphins can be made in response to stress, injury, and also
      pleasurable activities. In previous studies, it has been shown that levels of beta-endorphins
      in the blood go up during radiation therapy, and that this increase is linked to fatigue.
      This suggests that naltrexone may help to reduce fatigue in people who are getting radiation
      therapy In this research study, the investigators are looking to see whether naltrexone works
      better than a placebo in reducing fatigue during radiation therapy.
    

Eligibility criteria:

        Inclusion Criteria

        Eligibility Criteria for Monitoring Phase

          -  Age ≥ 18

          -  Diagnosis of: invasive breast cancer (stage I-III), ductal carcinoma in situ, lobular
             carcinoma in situ, lobular carcinoma

          -  Plan to receive radiation therapy

        Eligibility Criteria for Randomization Phase

          -  Participants may have had prior breast surgery and/or chemotherapy.

          -  Age ≥18 years.

             --Because no dosing or adverse event data are currently available on the use of
             naltrexone in cancer patients <18 years of age, children are excluded from this study,
             but will be eligible for future pediatric trials.

          -  Participants must have acceptable pre-treatment laboratory values as defined below:

               -  total bilirubin within normal institutional limits

               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

               -  creatinine within normal institutional limits OR

               -  creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above
                  institutional normal.

               -  If child-bearing potential, willingness to use adequate contraception (hormonal
                  or barrier method of birth control; abstinence) prior to study entry and for the
                  duration of study participation. Should a woman become pregnant or suspect she is
                  pregnant while she or her partner is participating in this study, she should
                  inform her treating physician immediately.

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Receiving radiation therapy of any type at DFCI, BWH, or MGH (including but not
             limited to partial breast irradiation, two-field, three-field, and four-field plans)

          -  FACIT-F subscale score >=10 pre-radiation therapy and decrease in FACIT-F of 10 points
             or more as compared to pre-radiotherapy baseline

        Exclusion Criteria:

        Exclusion Criteria for Monitoring Phase

          -  Suicidal ideation, as determined via PHQ-9

          -  Non-English speaking

        Exclusion Criteria for Randomization Phase

          -  Participants with major depressive disorder and/or suicidal ideation as determined by
             PHQ-9.

          -  Participants who are receiving any other investigational agents that might interact
             with study medication or influence the measurement of study outcomes.

          -  Participants with known metastatic disease should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to naltrexone.

          -  Participants who have used opioid-containing medications (including cough/cold
             medications containing codeine and/or antidiarrheals containing loperamide) in the
             past 2 weeks, or who are expected to require opioid-containing medications within the
             duration of the treatment period.

          -  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.

          -  Pregnant women are excluded from this study because naltrexone is category C agent
             with the potential for teratogenic or abortifacient effects. Because there is an
             unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with naltrexone, breastfeeding should be discontinued if the
             mother is treated with naltrexone.

          -  Participants using other contraindicated medications (thioridazine, yohimbine)