Precision Medicine Guided Treatment for Cancer Pain
Condition: Pain; CYP2D6 Polymorphism
MeSH terms: Cancer Pain
Study type: Interventional

Summary: 
      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.
    

Detailed 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.
    

Intervention name(s): CYP2D6; Brief Pain Inventory-Short Form (BPI-SF); M.D. Anderson Symptom Inventory (MDASI); OPRM1
Intervention type(s): Genetic; Behavioral; Behavioral; Genetic
Intervention description(s): Gentic testing for CYP2D6 metabolic pathway will be performed at baseline.; This questionnaire will be completed at baseline and weeks 2, 4, 6 and 8.; This questionnaire will be completed at baseline and weeks 2, 4, 6 and 8.; Genetic testing of the OPRM1 will be performed after week 8.
Other intervention name(s): cytochrome P450 2D6; µ-opioid receptor gene
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care