Metastatic Prostate Cancer
Conditions
Brief summary
The study is being done to see if a small daily dose of naltrexone (LDN, 3 mg pill) can help reduce tiredness (fatigue) in men with prostate cancer. All men in this study are being treated with hormone therapy (also called androgen deprivation therapy, or ADT). Some may also be taking newer hormone medicines such as apalutamide, daralutamide, enzalutamide, or abiraterone.
Detailed description
The purpose of this study is to learn if low dose naltrexone can safely improve energy and reduce fatigue in men receiving these treatments. Primary Objectives 1. Characterize mitochondrial bioenergetics, inflammation and oxidative stress after ADT and the remediating effects of LDN. 2. Assess the impact of low-dose naltrexone (LDN) on Cancer-related fatigue as measured by the FACIT-F questionnaire. Secondary Objectives 1. Evaluate quality of life (QOL) measures \[Functional Assessment of Cancer Therapy-Prostate (FACT-P) on subjects receiving LDN. 2. Evaluate safety and tolerability of LDN.
Interventions
DRUGNaltrexone
Naltrexone, a structurally similar compound to the opioid antagonist naloxone, but with longer half-life and higher bioavailability, was first synthesized in the 1960s and approved by Food and Drug Administration (FDA) in 1980s for treatment of opioid addiction. Its use was later expanded for management of alcohol addiction as well. The typical dose of naltrexone used for opioid and alcohol addiction is 50-100mg \[19\]. Naltrexone at one-tenth of the original addiction treatment dose, referred to as LDN, exhibits interesting paradoxical pharmacology and enhances endogenous opioid production. It also showed exhibiting multiple other pharmacological effects ranging from inhibition of proliferation of cancer cells, modulating immune response there by slowing the progression of autoimmune diseases and exhibiting the inhibitory effect of pro-inflammatory cytokines thereby reducing the symptoms of neuropathic and non-cancer related pain.
Sponsors
University of Arkansas
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
This is a single-center, single-arm study of low-dose naltrexone (LDN) in patients with metastatic prostate cancer, both castration-sensitive and castration-resistant, that have been on ADT for at least 3 months. Its overarching objective is to determine whether LDN can improve cancer-related fatigue and quality of life in this group of patients.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed biochemical recurrence and on ADT for at least 3 months. Metastatic castrate-sensitive and castrate-resistant prostate cancer on ADT with or without novel hormonal therapy like apalutamide, darolutamide, enzalutamide and abiraterone. * Initiation of hormonal ablative therapy within 3 months of registration. * ECOG performance status \<3. * Patients must have normal organ and marrow function as defined below: * leukocytes \>3,000/μL * absolute neutrophil count \>1,500/μL * platelets \>100,000/μL * total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal * creatinine ≤2.5.0 * left ventricular ejection fraction \>45% * FACIT-F score \< 43 on screening * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Prior chemotherapy received in the last three months. * Patients currently on PARP inhibitors. * Currently taking or have taken within 10 days of enrollment. * Patients may not be receiving any other investigational agents. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Naltrexone or other agents used in the study. * History of other malignancies other than nonmelanoma skin cancer, unless in complete remission and off therapy for that disease for at least 5 years. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Any Patient with acute hepatitis and liver failure are excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Characterize mitochondrial bioenergetics after ADT and the remediating effects of LDN | 30 months |
| Characterize inflammation after ADT and the remediating effects of LDN | 30 months |
| Characterize oxidative stress after ADT and the remediating effects of LDN | 30 months |
| Assess the impact of low-dose naltrexone (LDN) on Cancer-related fatigue as measured by the FACIT-F questionnaire | 30 months |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate quality of life (QOL) measures [Functional Assessment of Cancer Therapy-Prostate (FACT-P) on subjects receiving LDN | 30 months |
| Evaluate safety and tolerability of LDN by assessing the number of participants with treatment-related adverse events graded by CTCAE v5.0 | 30 months |
Countries
United States
Contacts
CONTACTAaron Holley
Outcome results
None listed