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

Naltrexone Randomized Controlled Trial for Treatment-Emergent Fatigue in Patients Receiving Radiation Therapy for Breast Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Ductal Carcinoma in Situ; Invasive Breast Cancer (Stage I-III); Lobular Carcinoma in Situ; Lobular Carcinoma; Fatigue Related to Cancer Treatment
• Intervention / Treatment: Drug: Naltrexone; Drug: Sugar Pill

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hosptial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Naltrexone; The treatment schedule includes a daily dose of naltrexone for 5 weeks. Treatment will be initiated at 25 mg/day during the first week to improve tolerability. The dose will be escalated to 50 mg/day after one week barring significant early improvement in fatigue or adverse events precluding dose escalation, and participants will continue to take 50 mg/day (or 25 mg/day if dose is not escalated) for 4 weeks to complete a 5-week treatment period.	Drug: Naltrexone; Other Names: ReVia®
Placebo Comparator: Sugar Pill; The treatment schedule includes a daily dose of equivalent placebo for 5 weeks. Treatment will be initiated at 25 mg/day during the first week to improve tolerability. The dose will be escalated to 50 mg/day after one week barring significant early improvement in fatigue or adverse events precluding dose escalation, and participants will continue to take 50 mg/day (or 25 mg/day if dose is not escalated) for 4 weeks to complete a 5-week treatment period.	Drug: Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FACIT-fatigue Subscale Score From Randomization to End of Study	Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-fatigue subscale): This 13-item self-report scale measuring fatigue and functional impairment as a result of fatigue has been validated in cancer patients (Cella et al. Cancer 2002;94:528-38) The scale is reverse-scored and the range is 0 (maximum fatigue) - 52 (minimum fatigue). According to ICD10 criteria, a score <= 34 indicates significant cancer related fatigue. A change of 10 points has been shown to constitute a clinically meaningful difference on this subscale.	Evaluated at baseline, weekly monitoring visits from start of radiation therapy and meets fatigue eligibility threshold

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Fremonta Meyer, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: May 10, 2014
• First Submitted That Met QC Criteria: May 10, 2014
• First Posted (Estimate): May 13, 2014

Study Record Updates

• Last Update Posted (Actual): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 12, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Ductal Carcinoma in Situ; Invasive Breast Cancer (Stage I-III); Lobular Carcinoma in Situ; Lobular Carcinoma; Fatigue Related to Cancer Treatment
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma in Situ; Breast Neoplasms; Fatigue; Carcinoma; Breast Carcinoma In Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: 14-056; R01CA150226 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No