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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02137252
Recruitment Status : Active, not recruiting
First Posted : May 13, 2014
Last Update Posted : February 12, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fremonta Meyer, MD, Dana-Farber Cancer Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Invasive Breast Cancer (Stage I-III) Ductal Carcinoma in Situ Lobular Carcinoma in Situ Lobular Carcinoma Fatigue Related to Cancer Treatment Drug: Naltrexone Drug: Sugar Pill Phase 2

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  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Official Title: Naltrexone Randomized Controlled Trial for Treatment-Emergent Fatigue in Patients Receiving Radiation Therapy for Breast Cancer
Study Start Date : May 2014
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fatigue

Arm Intervention/treatment
Experimental: Naltrexone
The treatment schedule includes a daily dose of double-blinded naltrexone vs. placebo for 5 weeks. Treatment will be initiated at 25 mg/day (or equivalent placebo) during the first week to improve tolerability. The dose will be escalated to 50 mg/day (or equivalent placebo) 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 Name: •ReVia®

No Intervention: Monitoring Phase
Brief self-report questionnaire (Functional Assessment of Chronic Illness Therapy-Fatigue Subscale; FACIT-F)
Placebo Comparator: Sugar Pill
daily dose placebo for 5 week treatment period
Drug: Sugar Pill

Primary Outcome Measures :
  1. Change in FACIT-fatigue subscale score from randomization to end of study [ Time Frame: baseline, week 5 ]

Other Outcome Measures:
  1. Changes in sleep continuity (sleep efficiency, total sleep time, sleep latency) from randomization to end of study [ Time Frame: baseline, week 5 ]
    Pittsburgh Sleep Quality Index, Insomnia Severity Index

  2. Changes in quality of life measures from randomization to end of study [ Time Frame: baseline, week 5 ]
    Functional Assessment of Cancer Therapy-Breast Subscale Functional Assessment of Cancer Therapy-Endocrine Symptoms Subscale

  3. Change in depression from randomization to end of study [ Time Frame: baseline, week 5 ]
    Patient Health Questionnaire-9

  4. Change in anxiety from randomization to end of study [ Time Frame: baseline, week 5 ]
    Generalized Anxiety Disorder-7

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02137252

United States, Massachusetts
Massachusetts General Hosptial
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Fremonta Meyer, MD Dana-Farber Cancer Institute

Responsible Party: Fremonta Meyer, MD, Principal Investigator, Dana-Farber Cancer Institute Identifier: NCT02137252     History of Changes
Other Study ID Numbers: 14-056
R01CA150226 ( U.S. NIH Grant/Contract )
First Posted: May 13, 2014    Key Record Dates
Last Update Posted: February 12, 2018
Last Verified: February 2018

Keywords provided by Fremonta Meyer, MD, Dana-Farber Cancer Institute:
Invasive Breast Cancer (Stage I-III)
Ductal Carcinoma in Situ
Lobular Carcinoma in Situ
Lobular Carcinoma
Fatigue Related to Cancer Treatment

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma in Situ
Carcinoma, Ductal
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Lobular
Breast Carcinoma In Situ
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Breast Diseases
Skin Diseases
Signs and Symptoms
Neoplasms, Ductal, Lobular, and Medullary
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents