Precision Medicine Guided Treatment for Cancer Pain
2 other identifiers
interventional
63
1 country
2
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable pain
Started Apr 2016
Longer than P75 for not_applicable pain
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 22, 2016
CompletedFirst Posted
Study publicly available on registry
January 27, 2016
CompletedStudy Start
First participant enrolled
April 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 10, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
January 10, 2019
CompletedJanuary 14, 2019
January 1, 2019
2.8 years
January 22, 2016
January 10, 2019
Conditions
Outcome Measures
Primary Outcomes (2)
Brief Pain Inventory-Short Form (BPI-SF) will be used to evaluate pain management and interference between the groups.
Brief Pain Inventory-Short Form (BPI-SF) is a 9 item self-administered questionnaire used to evaluate the severity of a patient's pain and the impact of this pain on the patient's daily functioning. This is a 10-point scale with 0 being the best possible score, meaning "no pain", and 10 being the worst possible score, meaning "pain as bad as you can imagine".
Change in baseline, weeks 2, 4, 6 and 8.
MD Anderson Symptom Inventory (MDASI) will be used to evaluate symptom interference between the groups.
MD Anderson Symptom Inventory (MDASI) modules augment the 19 core MDASI symptom and interference items with additional items identified as unique to a particular patient population. This is a 10-point scale with 0 being the best possible score, meaning "did not interfere" and 10 being the worst possible score, meaning "interfered completely".
Change in baseline, weeks 2, 4, 6 and 8.
Secondary Outcomes (3)
Observe Differences in Pain Control and Pain Interference between the number of participants based on OPRM1 Genotype
week 8
Observe Differences in Symptom Interference between the number of participants based on OPRM1 Genotype
week 8
Observe Differences in Opioid Doses between the number of participants based on OPRM1 Genotype
week 8
Study Arms (2)
Genotype Arm
EXPERIMENTALParticipants 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).
Traditional Arm
ACTIVE COMPARATORParticipants 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).
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
University of Florida
Gainesville, Florida, 32611, United States
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33607, United States
Related Publications (2)
Mosley SA, Cicali E, Del Cueto A, Portman DG, Donovan KA, Gong Y, Langaee T, Gopalan P, Schmit J, Starr JS, Silver N, Chang YD, Rajasekhara S, Smith JE, Soares HP, Clare-Salzler M, Starostik P, George TJ, McLeod HL, Fillingim RB, Hicks JK, Cavallari LH. CYP2D6-guided opioid therapy for adults with cancer pain: A randomized implementation clinical trial. Pharmacotherapy. 2023 Dec;43(12):1286-1296. doi: 10.1002/phar.2875. Epub 2023 Sep 21.
PMID: 37698371DERIVEDMosley SA, Hicks JK, Portman DG, Donovan KA, Gopalan P, Schmit J, Starr J, Silver N, Gong Y, Langaee T, Clare-Salzler M, Starostik P, Chang YD, Rajasekhara S, Smith JE, Soares HP, George TJ Jr, McLeod HL, Cavallari LH. Design and rational for the precision medicine guided treatment for cancer pain pragmatic clinical trial. Contemp Clin Trials. 2018 May;68:7-13. doi: 10.1016/j.cct.2018.03.001. Epub 2018 Mar 10.
PMID: 29535047DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Larisa H Cavallari, PharmD
University of Florida
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- SUPPORTIVE CARE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 22, 2016
First Posted
January 27, 2016
Study Start
April 1, 2016
Primary Completion
January 10, 2019
Study Completion
January 10, 2019
Last Updated
January 14, 2019
Record last verified: 2019-01