Precision Medicine Guided Treatment for Cancer Pain

Status:	Completed
Conditions:	Chronic Pain
Therapuetic Areas:	Musculoskeletal
Healthy:	No
Age Range:	18 - 120
Updated:	1/16/2019
Start Date:	April 2016
End Date:	January 10, 2019

Pain is one of the most burdensome symptoms associated with cancer and its treatment, and
opioids are the cornerstone of clinical pain management in cancer patients. Yet, individual
patient responses to opioids vary widely, and the patient's genotype contributes to this
variability. Specifically, cytochrome P450 2D6 (CYP2D6) genotype has important relevance for
response to opioid analgesics that depend on CYP2D6 for bioactivation. Poor metabolizers
(PMs) have lower concentrations of active metabolites of codeine (morphine), tramadol
(O-desmethyltramadol), oxycodone (oxymorphone), and hydrocodone (hydromorphone), compared to
extensive metabolizers (EMs). Morphine and O-desmethyltramadol have 200-fold greater affinity
for the µ-opioid receptor than the parent compound, whereas oxymorphone and hydromorphone
have 40-fold and 10-fold higher receptor affinity compared to their parent compounds,
respectively. Consequently, PMs may fail to derive pain relief from these opioids compared to
EMs. Interestingly, the occurrence of side effects may not differ between PMs and EMs so that
while PMs may get little to no pain relief from certain opioid analgesics, they may still
experience troublesome adverse effects. Intermediate metabolizers (IMs) are also expected to
have reduced analgesic response based on their significant reduction in enzyme activity.
Conversely, individuals with the UM phenotype may have toxic concentrations of active opioid
metabolites, with reports of life-threatening toxicity and death. The µ-opioid receptor gene
(OPRM1) is the primary binding site for endogenous opioid peptides and opioid analgesics, and
may have additional contributions to opioid response. The investigators propose to examine
the effect of CYP2D6 genotype-guided pain management on cancer pain control in study
participants and the additional effect of the OPRM1 genotype on response to opioids.

This will be a randomized, open label, multi-site clinical trial conducted in UF Health
Cancer Center in Gainesville, FL and in Moffitt Cancer Center in Tampa, FL. Each site will be
responsible for overseeing patient care and research at their respective facility. This
research will examine pain-related outcomes with CYP2D6-guided cancer pain management for
study participants. In addition, the investigators will evaluate a prospective cohort study
in the same population examining the effect of OPRM1 genetic variants on pain relief and
adverse drug effects over time.

Participants will be randomized in a 1:1 manner to receive CYP2D6 genotype-guided (n=50) or
non-genotype-guided (traditional, n=50) selection of pain medication. Patients in the
genotype arm will be genotyped at baseline for CYP2D6 variants. Participants will fill out
the the Brief Pain Inventory-Short Form (BPI-SF) and M.D. Anderson Symptom Inventory (MDASI)
questionnaires at baseline. Then, during the clinical visits the same questionnaires will be
done during weeks 2, 4, 6, and 8 or by telephone or electronic survey.

Inclusion Criteria:

- Diagnosis of histologically or cytologically proven solid tumor with or without
metastasis

- Receiving treatment at UF Health Cancer Center for outpatient pain management with an
opioid

Exclusion Criteria:

- Undergone surgery within the last three months or are scheduled to undergo surgery
during the study period (4 weeks)

- Documented psychiatric or neurological condition that would interfere with study
participation

- Liver transplant

- Allergic to opioids

We found this trial at

sites

H. Lee Moffitt Cancer Center & Research Institute

12902 USF Magnolia Dr
Tampa, Florida 33612

(888) 663-3488