Naltrexone RCT for Treatment-Emergent Fatigue in Patients Receiving Radiation Therapy for Breast Cancer

This trial has two phases (a monitoring and an intervention phase).

Monitoring Phase: Prior to starting radiotherapy for non-metastatic breast cancer,
participants will be approached and consented for the monitoring phase of the study, which
involves longitudinal monitoring of fatigue in order to establish whether a patient develops
fatigue after starting radiation. The level of pre-radiotherapy fatigue will be obtained
during the final two weeks before radiotherapy is started. All participants will undergo
weekly monitoring of fatigue via a brief self-report questionnaire. The monitoring period
will continue up until one month after the conclusion of radiotherapy. Those whose fatigue
symptoms increase above the pre-specified threshold at any point during the monitoring period
will be approached about enrollment into the intervention phase of the study.

Intervention Phase: This is a randomized, double-blind, parallel-arm 5-week clinical trial
which will be used to determine the effect of naltrexone on fatigue emerging during radiation
therapy for non-metastatic breast cancer.

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)