PainNCT02664350
Precision Medicine Guided Treatment for Cancer Pain
A study testing CYP2D6, Brief Pain Inventory-Short Form (BPI-SF) and M.D. Anderson Symptom Inventory (MDASI) in people with Pain and CYP2D6 Polymorphism, run by University of Florida at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Pain, CYP2D6 Polymorphism
- What is being tested?
- CYP2D6, Brief Pain Inventory-Short Form (BPI-SF) and M.D. Anderson Symptom Inventory (MDASI)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2016to 10 Jan 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
2 sites in 1 country.
United States2 sites
University of Florida
Gainesville, Florida, 32611
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33607
About this study
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.
Read the 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.
- Conditions
- Pain, CYP2D6 Polymorphism
- Being tested
- CYP2D6, Brief Pain Inventory-Short Form (BPI-SF), M.D. Anderson Symptom Inventory (MDASI), OPRM1
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYP2D6Genetic
Also called cytochrome P450 2D6
Gentic testing for CYP2D6 metabolic pathway will be performed at baseline.
Brief Pain Inventory-Short Form (BPI-SF)Behavioural
This questionnaire will be completed at baseline and weeks 2, 4, 6 and 8.
M.D. Anderson Symptom Inventory (MDASI)Behavioural
This questionnaire will be completed at baseline and weeks 2, 4, 6 and 8.
OPRM1Genetic
Also called µ-opioid receptor gene
Genetic testing of the OPRM1 will be performed after week 8.
| Study group | Role | What they receive |
|---|---|---|
| Genotype Arm | Experimental | 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). Receives: Genetic: CYP2D6; Behavioral: Brief Pain Inventory-Short Form (BPI-SF); Behavioral: M.D. Anderson Symptom Inventory (MDASI); Genetic: OPRM1 |
| Traditional Arm | Active comparator | 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). Receives: Genetic: CYP2D6; Behavioral: Brief Pain Inventory-Short Form (BPI-SF); Behavioral: M.D. Anderson Symptom Inventory (MDASI); Genetic: OPRM1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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".
Measured: 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".
Measured: 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
At the end of the study, all participants will be genotyped for OPRM1 and evaluated for pain control (as assessed by the BPI-SF).
Measured: week 8
Observe Differences in Symptom Interference between the number of participants based on OPRM1 Genotype
At the end of the study, all participants will be genotyped for OPRM1 and evaluated for symptom interference (as assessed by the MDASI).
Measured: week 8
Observe Differences in Opioid Doses between the number of participants based on OPRM1 Genotype
At the end of the study, all participants will be genotyped for OPRM1 and evaluated for opioid dose (as assessed in morphine equivalent doses).
Measured: week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2016 (estimated)
- Study startApr 2016
- Primary completion10 Jan 2019
- Study completion10 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Larisa H Cavallari, PharmD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02664350
- Sponsor's protocol ID
- IRB201500780
- Other IDs
- OCR16264
- Status last verified
- Jan 2019
- First submitted
- 22 Jan 2016
- Last updated
- 14 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 37698371Mosley 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.
PubMed 29535047
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Medicine Guided Treatment for Cancer Pain
- ClinicalTrials.gov ID
- NCT02664350
- Acronym / sponsor ID
- IRB201500780
- Conditions
- Pain, CYP2D6 Polymorphism
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Apr 2016
- Primary completion
- 10 Jan 2019 (actual)
- Study completion
- 10 Jan 2019 (actual)
- First posted
- 27 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Genotype Arm | Experimental | Genetic: CYP2D6, Behavioral: Brief Pain Inventory-Short Form (BPI-SF), Behavioral: M.D. Anderson Symptom Inventory (MDASI), Genetic: OPRM1Participants 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 comparator | Genetic: CYP2D6, Behavioral: Brief Pain Inventory-Short Form (BPI-SF), Behavioral: M.D. Anderson Symptom Inventory (MDASI), Genetic: OPRM1Participants 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). |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CYP2D6Also: cytochrome P450 2D6Gentic testing for CYP2D6 metabolic pathway will be performed at baseline. | Genetic | Genotype Arm, Traditional Arm |
| Brief Pain Inventory-Short Form (BPI-SF)This questionnaire will be completed at baseline and weeks 2, 4, 6 and 8. | Behavioural | Genotype Arm, Traditional Arm |
| M.D. Anderson Symptom Inventory (MDASI)This questionnaire will be completed at baseline and weeks 2, 4, 6 and 8. | Behavioural | Genotype Arm, Traditional Arm |
| OPRM1Also: µ-opioid receptor geneGenetic testing of the OPRM1 will be performed after week 8. | Genetic | Genotype Arm, Traditional Arm |
Primary outcome
Brief Pain Inventory-Short Form (BPI-SF) will be used to evaluate pain management and interference between the groups.
Time frame: Change in baseline, weeks 2, 4, 6 and 8.
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".
MD Anderson Symptom Inventory (MDASI) will be used to evaluate symptom interference between the groups.
Time frame: Change in baseline, weeks 2, 4, 6 and 8.
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".
3 secondary outcomes
Observe Differences in Pain Control and Pain Interference between the number of participants based on OPRM1 Genotype
Time frame: week 8
Observe Differences in Symptom Interference between the number of participants based on OPRM1 Genotype
Time frame: week 8
Observe Differences in Opioid Doses between the number of participants based on OPRM1 Genotype
Time frame: week 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2019.
- Derived from this study: PubMed 37698371Mosley 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.
- Derived from this study: PubMed 29535047Mosley 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Larisa H Cavallari, PharmD principal investigator
University of Florida
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CYP2D6, Brief Pain Inventory-Short Form (BPI-SF) and M.D. Anderson Symptom Inventory (MDASI) in people with Pain and CYP2D6 Polymorphism, run by University of Florida at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brief Pain Inventory-Short Form (BPI-SF) will be used to evaluate pain management and interference between the groups. (time frame: Change in baseline, weeks 2, 4, 6 and 8.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02664350, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2019.