Malignant Tumor of Ill-defined Site
Conditions
Brief summary
About half of all cancer patients seen in oncology clinics have pain at initial assessment; pain relief within a one-month period is seen in approximately one third of these patients and pain worsening in about one fifth. Risk factors for under-treatment of cancer pain include age older than 65 years, minority status, and inadequate pain assessment practices. There is a need for better methods of opioid drug/dose selection and identification of risk factors for worsening pain. Pharmacogenomic approaches offer insight into the genetic variables that impact the pharmacokinetic and pharmacodynamic behavior of opioids. Translating pharmacogenomic results into actionable prescribing decisions may ultimately enable a personalized approach to pain management, increasing the chance of significant pain improvement. Cancer outpatients with uncontrolled malignant pain will be offered a pharmacogenomic test through participation in the study. The results of this test will be used to modify their pain regimen, if applicable.
Detailed description
All subjects will be assessed and prescribed a pain regimen as part of standard practice at the initial visit. Subjects will provide a buccal swab for pharmacogenomic testing and will be discharged on their initial pain regimen. After the initial visit, subjects will be asked to rate their daily pain on a scale of 0-10. A coordinator will follow up with the subject within 7 days (Assessment #1). Subjects will be asked to report information about their pain scores, pain medication use, and caffeine intake, in addition to any bothersome symptoms. Subjects who continue to have uncontrolled pain, are experiencing bothersome symptoms, and/or requests for a drug/dose modification will have his/her drug/dose modified using the pharmacogenomic test results. If the subject has had significant pain improvement, stable mild pain and/or is satisfied with their level of pain at the assessment (regardless of pain score), he/she will be recommended to continue the current drug/dose and return to clinic on day 30 for the final follow-up. Subjects will be told to call if their pain becomes intolerable or if they experience bothersome symptoms after Assessment #1 for further drug/dose modification if needed prior to day 30. The coordinator will follow up with the subjects receiving a drug/dose modification after another 7 days (Assessment #2). Subjects who have now had significant pain improvement, stable mild pain, and/or are satisfied with their level pain at the assessment (regardless of pain score) will continue on the same regimen. If the subjects' pain is still uncontrolled, they are experiencing bothersome symptoms, and/or they request a drug/dose modification, their drug/dose will be modified accordingly. Subjects will be told to call if needed, otherwise they will be seen in clinic on day 30 (Final Assessment). If the subject experiences intolerable pain prior to any scheduled assessment, the subject will call for appropriate drug/dose modification.
Interventions
GENETICPharmacogenomic Testing
Pharmacogenomic test results to guide drug/dose modifications
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Enrolled subjects all receive pharmacogenomic testing with the intention of guiding pain management. This single-arm trial is testing against a published historical control.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Presence of uncontrolled malignant pain (score of greater than or equal to 2 on an 11 point scale \[0-10\]) as diagnosed and assessed by the Investigator, using the Edmonton Symptom Assessment Scale (ESAS). * Documentation of any stage of cancer of any tumor location (solid or hematological). * At least 18 years of age. * Either nociceptive or neuropathic pain. * Able to understand and be willing to sign the study consent form.
Exclusion criteria
* Inpatient service at baseline visit. * Significant dysphagia and inability to swallow oral medications as determined by the Investigator. * Active or recent (within one year) drug and/or alcohol abuse as determined by the Investigator. * Significant baseline cognitive impairment, as determined by the Investigator. Known (anaphylactic) hypersensitivity to any opioid. * Severe oral mucositis that would impair proper buccal testing as determined by the Investigator. * Receiving concurrent rehabilitation medicine care, nociception modulation (e.g., electrical stimulation), use of modalities with physiologic effects that indirectly influence nociception (e.g., light, laser therapy), or any other non-pharmacologic approaches to pain management other than exercise, rest, ice, compression, and elevation (RICE). * Presence of major psychiatric disorders as determined by the Investigator. * Receiving active treatment or prophylaxis for epilepsy. * Unable or unwilling to sign the study consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Pain Improvement as Measured Using the Edmonton Symptom Assessment Scale (ESAS) From Baseline Assessment (Day 0) to Final Assessment on Day 30 +/- 7 | Enrollment to Final Assessment (30 +/- 7 days from Baseline Assessment (Day 0)) | Proportion of subjects achieving significant pain improvement over a one month period (30 days +/- 7) (defined as a ≥ 2 point decrease from baseline pain score on an 11-point scale \[0-10\]) in oncology outpatients receiving pharmacogenomic testing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Morphine Equivalent Daily Doses (MEDD) in Milligrams | Final Assessment (30 +/- 7 days from Baseline Assessment (Day 0)) | Describe the distribution of morphine equivalent daily dose (MEDD) in the evaluable population. The MEDD was calculated and recorded at the Final Assessment for each subject by converting the subject's total daily opioid consumption at the Final Assessment to morphine equivalent doses using the following website: http://www.globalrph.com/narcoticonv.htm (widely used across many health systems for drug/dose conversions and fully referenced). |
| Percentage of Subjects With an Actionable Genotype, Defined as the Presence of Any Mutation(s) That is (Are) Used to Guide a Drug/Dose Modification | Enrollment to Final Assessment (30 +/- 7 days from Baseline Assessment (Day 0)) | An actionable genotype is defined as the presence of at least one mutation that is used to guide a drug/dose modification during Assessment 1, Assessment 2, or any unscheduled visit. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pharmacogenomic Testing Cancer outpatients with uncontrolled malignant pain undergo a pharmacogenomic panel (by buccal swab) with the intent of informing pain management. | 75 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Pharmacogenomic Testing |
|---|---|
| Age, Continuous | 61 years |
| Cancer type Breast | 14 Participants |
| Cancer type Cutaneous malignancies | 6 Participants |
| Cancer type Gastrointestinal | 12 Participants |
| Cancer type Genitourinary | 5 Participants |
| Cancer type Gynecologic | 8 Participants |
| Cancer type Multiple Myeloma | 11 Participants |
| Cancer type Other | 9 Participants |
| Cancer type Thoracic | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 58 Participants |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 31 Participants |
| Stage of cancer (as captured from the Medical Record and determined by the TNM system of the AJCC) 1 or 2 | 13 Participants |
| Stage of cancer (as captured from the Medical Record and determined by the TNM system of the AJCC) 3 or 4 | 57 Participants |
| Stage of cancer (as captured from the Medical Record and determined by the TNM system of the AJCC) Other | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 75 |
| other Total, other adverse events | 34 / 75 |
| serious Total, serious adverse events | 2 / 75 |
Outcome results
Primary
Rate of Pain Improvement as Measured Using the Edmonton Symptom Assessment Scale (ESAS) From Baseline Assessment (Day 0) to Final Assessment on Day 30 +/- 7
Proportion of subjects achieving significant pain improvement over a one month period (30 days +/- 7) (defined as a ≥ 2 point decrease from baseline pain score on an 11-point scale \[0-10\]) in oncology outpatients receiving pharmacogenomic testing.
Time frame: Enrollment to Final Assessment (30 +/- 7 days from Baseline Assessment (Day 0))
Population: The evaluable population is defined as those enrolled subjects providing pain scores at Baseline Assessment (Day 0) and Final Assessment (Day 30 +/- 7).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pharmacogenomic Testing: Evaluable Population | Rate of Pain Improvement as Measured Using the Edmonton Symptom Assessment Scale (ESAS) From Baseline Assessment (Day 0) to Final Assessment on Day 30 +/- 7 | .5556 proportion of evaluable participants |
Comparison: A single-stage design was used to test the hypothesis that the pain improvement rate, assessed by the Edmonton Symptom Assessment Scale, is \<= 0.30. Our study targeted enrollment of 71 evaluable subjects for the final analysis; 54 subjects met the criteria at study closure. Assuming a one-sided alpha=0.10 significance level, 71 evaluable subjects would provide approximately 90% power to reject the null hypothesis (based on an exact binomial test) assuming the true pain improvement rate is 0.45.p-value: <0.000195% CI: [0.414, 0.6908]Exact binomial test of proportions
Secondary
Morphine Equivalent Daily Doses (MEDD) in Milligrams
Describe the distribution of morphine equivalent daily dose (MEDD) in the evaluable population. The MEDD was calculated and recorded at the Final Assessment for each subject by converting the subject's total daily opioid consumption at the Final Assessment to morphine equivalent doses using the following website: http://www.globalrph.com/narcoticonv.htm (widely used across many health systems for drug/dose conversions and fully referenced).
Time frame: Final Assessment (30 +/- 7 days from Baseline Assessment (Day 0))
Population: The evaluable population is defined as those enrolled subjects providing pain scores at Baseline Assessment (Day 0) and Final Assessment (Day 30 +/- 7).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pharmacogenomic Testing: Evaluable Population | Morphine Equivalent Daily Doses (MEDD) in Milligrams | 90 milligrams |
Secondary
Percentage of Subjects With an Actionable Genotype, Defined as the Presence of Any Mutation(s) That is (Are) Used to Guide a Drug/Dose Modification
An actionable genotype is defined as the presence of at least one mutation that is used to guide a drug/dose modification during Assessment 1, Assessment 2, or any unscheduled visit.
Time frame: Enrollment to Final Assessment (30 +/- 7 days from Baseline Assessment (Day 0))
Population: The evaluable population is defined as those enrolled subjects providing pain scores at Baseline Assessment (Day 0) and Final Assessment (Day 30 +/- 7).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pharmacogenomic Testing: Evaluable Population | Percentage of Subjects With an Actionable Genotype, Defined as the Presence of Any Mutation(s) That is (Are) Used to Guide a Drug/Dose Modification | 33.33 percentage of evaluable participants |