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Precision Medicine Guided Treatment for Cancer Pain

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University of Florida

Status

Completed

Conditions

CYP2D6 Polymorphism
Pain

Treatments

Genetic: CYP2D6
Behavioral: Brief Pain Inventory-Short Form (BPI-SF)
Behavioral: M.D. Anderson Symptom Inventory (MDASI)
Genetic: OPRM1

Study type

Interventional

Funder types

Other

Identifiers

NCT02664350
IRB201500780
OCR16264 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

63 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Supportive Care

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

63 participants in 2 patient groups

Genotype Arm
Experimental group
Description:
Participants in this arm will have genotyping performed for CYP2D6 variants. Based on the CYP2D6 the treating physicians will be provided with an interpretation of genotype results, and a recommendation will be provided by a pharmacist on the UF Health Personalized Medicine team through one-on-one consultation with the physician for the type of pain medication. These participants will also be genotyped for OPRM1 variants at the end of the study which is performed for research purposes only. In addition, they will fill out the following questionnaires Brief Pain Inventory-Short Form (BPI-SF) and M.D. Anderson Symptom Inventory (MDASI).
Treatment:
Genetic: OPRM1
Behavioral: M.D. Anderson Symptom Inventory (MDASI)
Behavioral: Brief Pain Inventory-Short Form (BPI-SF)
Genetic: CYP2D6
Traditional Arm
Active Comparator group
Description:
Participants in this arm will have genotyping for CYP2D6 and OPRM1, however this information will not be provided to the physicians for treatment of the analgesic therapy but will be used for research purposes only. In addition, they will fill out the following questionnaires Brief Pain Inventory-Short Form (BPI-SF) and M.D. Anderson Symptom Inventory (MDASI).
Treatment:
Genetic: OPRM1
Behavioral: M.D. Anderson Symptom Inventory (MDASI)
Behavioral: Brief Pain Inventory-Short Form (BPI-SF)
Genetic: CYP2D6

Trial contacts and locations

2

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Data sourced from clinicaltrials.gov

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