LCI-NOS-PAIN-001: A Prospective, Pharmacogenomic-Driven Study of Pain Management in Oncology Outpatients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pharmacogenomic Testing Pharmacogenomic test results to guide drug/dose modifications |
Genetic: Pharmacogenomic Testing
Pharmacogenomic test results to guide drug/dose modifications
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Levine Cancer Institute | Charlotte | North Carolina | United States | 28204 |
Sponsors and Collaborators
- Wake Forest University Health Sciences
Investigators
- Principal Investigator: Jai Patel, PharmD, Levine Cancer Institute
Study Documents (Full-Text)
More Information
Publications
None provided.- LCI-NOS-PAIN-001
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Pharmacogenomic Testing |
|---|---|
| Arm/Group Description | Cancer outpatients with uncontrolled malignant pain undergo a pharmacogenomic panel (by buccal swab) with the intent of informing pain management. |
| Period Title: Overall Study | |
| STARTED | 75 |
| COMPLETED | 59 |
| NOT COMPLETED | 16 |
Baseline Characteristics
| Arm/Group Title | Pharmacogenomic Testing |
|---|---|
| Arm/Group Description | Cancer outpatients with uncontrolled malignant pain undergo a pharmacogenomic panel (by buccal swab) with the intent of informing pain management. |
| Overall Participants | 75 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
61
|
| Sex: Female, Male (Count of Participants) | |
| Female |
44
58.7%
|
| Male |
31
41.3%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
16
21.3%
|
| White |
58
77.3%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
1
1.3%
|
| Cancer type (Count of Participants) | |
| Breast |
14
18.7%
|
| Gastrointestinal |
12
16%
|
| Gynecologic |
8
10.7%
|
| Multiple Myeloma |
11
14.7%
|
| Thoracic |
10
13.3%
|
| Genitourinary |
5
6.7%
|
| Cutaneous malignancies |
6
8%
|
| Other |
9
12%
|
| Stage of cancer (as captured from the Medical Record and determined by the TNM system of the AJCC) (Count of Participants) | |
| 1 or 2 |
13
17.3%
|
| 3 or 4 |
57
76%
|
| Other |
5
6.7%
|
Outcome Measures
| Title | 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 |
|---|---|
| Description | 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)) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The evaluable population is defined as those enrolled subjects providing pain scores at Baseline Assessment (Day 0) and Final Assessment (Day 30 +/- 7). |
| Arm/Group Title | Pharmacogenomic Testing: Evaluable Population |
|---|---|
| Arm/Group Description | Enrolled subjects providing pain scores at Baseline Assessment (Day 0) and Final Assessment (Day 30 +/- 7). |
| Measure Participants | 54 |
| Number (95% Confidence Interval) [proportion of evaluable participants] |
.5556
0.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pharmacogenomic Testing: Evaluable Population |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | It has been reported that, based on the Edmonton Symptom Assessment Scale (ESAS) pain scale, about 30% of cancer patients receiving standard of care pain management experienced >= 2-point improvement in pain score between visits [Ref]. Ref: Scharpf, J., et al., The role of pain in head and neck cancer recurrence and survivorship. Arch Otolaryngol Head Neck Surg, 2009. 135(8): p. 789-94. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The a priori threshold for statistical significance was alpha = 0.10. | |
| Method | Exact binomial test of proportions | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Exact binomial proportion |
| Estimated Value | .5556 | |
| Confidence Interval |
(2-Sided) 95% .4140 to .6908 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Morphine Equivalent Daily Doses (MEDD) in Milligrams |
|---|---|
| Description | 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)) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The evaluable population is defined as those enrolled subjects providing pain scores at Baseline Assessment (Day 0) and Final Assessment (Day 30 +/- 7). |
| Arm/Group Title | Pharmacogenomic Testing: Evaluable Population |
|---|---|
| Arm/Group Description | Enrolled subjects providing pain scores at baseline assessment and a final assessment within 30 +/- 7 days. |
| Measure Participants | 54 |
| Median (Full Range) [milligrams] |
90
|
| Title | 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 |
|---|---|
| Description | 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)) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The evaluable population is defined as those enrolled subjects providing pain scores at Baseline Assessment (Day 0) and Final Assessment (Day 30 +/- 7). |
| Arm/Group Title | Pharmacogenomic Testing: Evaluable Population |
|---|---|
| Arm/Group Description | Enrolled subjects providing pain scores at baseline assessment and a final assessment within 30 +/- 7 days. |
| Measure Participants | 54 |
| Number (95% Confidence Interval) [percentage of evaluable participants] |
33.33
44.4%
|
Adverse Events
| Time Frame | From enrollment date (i.e., buccal swab is collected) (Day 0) to the final study assessment on Day 30 +/- 7. | |
|---|---|---|
| Adverse Event Reporting Description | Opioid-related adverse events were summarized and attributed based on Common Terminology Criteria for Adverse Events version 4.03. Adverse events deemed "possibly", "probably", and "definitely related" to opioid use by the Investigator were summarized for the study. | |
| Arm/Group Title | Pharmacogenomic Testing | |
| Arm/Group Description | Cancer outpatients with uncontrolled malignant pain undergo a pharmacogenomic panel (by buccal swab) with the intent of informing pain management. | |
All Cause Mortality |
||
| Pharmacogenomic Testing | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/75 (2.7%) | |
Serious Adverse Events |
||
| Pharmacogenomic Testing | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/75 (2.7%) | |
| General disorders | ||
| Death NOS | 2/75 (2.7%) | 2 |
Other (Not Including Serious) Adverse Events |
||
| Pharmacogenomic Testing | ||
| Affected / at Risk (%) | # Events | |
| Total | 34/75 (45.3%) | |
| Gastrointestinal disorders | ||
| Constipation | 7/75 (9.3%) | 8 |
| Dry mouth | 1/75 (1.3%) | 1 |
| Gastroesophageal reflux disease | 1/75 (1.3%) | 1 |
| Nausea | 13/75 (17.3%) | 14 |
| Vomiting | 5/75 (6.7%) | 5 |
| General disorders | ||
| Fatigue | 7/75 (9.3%) | 9 |
| Gait disturbance | 1/75 (1.3%) | 1 |
| General disorders and administration site conditions - Other, Weakness in joints | 1/75 (1.3%) | 1 |
| Injury, poisoning and procedural complications | ||
| Fall | 3/75 (4%) | 3 |
| Injury, poisoning and procedural complications - Other, Chin laceration | 1/75 (1.3%) | 1 |
| Nervous system disorders | ||
| Cognitive disturbance | 1/75 (1.3%) | 1 |
| Concentration impairment | 1/75 (1.3%) | 3 |
| Dizziness | 6/75 (8%) | 6 |
| Headache | 2/75 (2.7%) | 3 |
| Hypersomnia | 1/75 (1.3%) | 1 |
| Nervous system disorders - Other, Change in mental status | 2/75 (2.7%) | 2 |
| Neuralgia | 1/75 (1.3%) | 1 |
| Somnolence | 2/75 (2.7%) | 2 |
| Psychiatric disorders | ||
| Confusion | 6/75 (8%) | 6 |
| Delirium | 2/75 (2.7%) | 2 |
| Hallucinations | 2/75 (2.7%) | 2 |
| Skin and subcutaneous tissue disorders | ||
| Pruritus | 2/75 (2.7%) | 3 |
| Rash acneiform | 1/75 (1.3%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Danielle M Boselli |
|---|---|
| Organization | Atrium Health/Levine Cancer Institute, Department of Cancer Biostatistics |
| Phone | 12017903385 |
| Danielle.Boselli@AtriumHealth.org |
- LCI-NOS-PAIN-001