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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2014 by Dana-Farber Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fremonta Meyer, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT02137252
First received: May 10, 2014
Last updated: NA
Last verified: May 2014
History: No changes posted
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: Naltrexone Randomized Controlled Trial for Treatment-Emergent Fatigue in Patients Receiving Radiation Therapy for Breast Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Change in FACIT-fatigue subscale score from randomization to end of study [ Time Frame: baseline, week 5 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Changes in sleep continuity (sleep efficiency, total sleep time, sleep latency) from randomization to end of study [ Time Frame: baseline, week 5 ] [ Designated as safety issue: No ]
    Pittsburgh Sleep Quality Index, Insomnia Severity Index

  • Changes in quality of life measures from randomization to end of study [ Time Frame: baseline, week 5 ] [ Designated as safety issue: No ]
    Functional Assessment of Cancer Therapy-Breast Subscale Functional Assessment of Cancer Therapy-Endocrine Symptoms Subscale

  • Change in depression from randomization to end of study [ Time Frame: baseline, week 5 ] [ Designated as safety issue: No ]
    Patient Health Questionnaire-9

  • Change in anxiety from randomization to end of study [ Time Frame: baseline, week 5 ] [ Designated as safety issue: No ]
    Generalized Anxiety Disorder-7


Estimated Enrollment: 300
Study Start Date: May 2014
Estimated Study Completion Date: April 2022
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02137252

Contacts
Contact: Fremonta Meyer, MD 617-632-6181 flmeyer@partners.org

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Fremonta Meyer, MD    617-632-4566    flmeyer@partners.org   
Principal Investigator: Fremota Meyer, MD         
Massachusetts General Hosptial Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Alphonse Taghian, MD, PhD    617-726-7559    ataghian@partners.org   
Principal Investigator: Alphonse Taghian, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Fremonta Meyer, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Fremonta Meyer, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02137252     History of Changes
Other Study ID Numbers: 14-056, R01CA150226
Study First Received: May 10, 2014
Last Updated: May 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by 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
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Fatigue
Carcinoma, Lobular
Carcinoma, Ductal, Breast
Carcinoma, Ductal
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Signs and Symptoms
Naltrexone
Narcotic Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014