Implementation of Personalized Medicine for Optimal Drug Therapy in Cancer

Study Overview
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Brief Summary
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A prospective longitudinal cohort study that will assess the effect of a Personalized Medicine (PM) clinic recommendations on pharmacogenetic variation and/or interacting drugs on plasma drug exposure, effectiveness or toxicity of commonly used antidepressant, pain, and antiemetic medications in cancer patients. Such recommendations will entail genotype-guided treatment suggestions while also considering potential DDI, and will be provided to patients during their clinic visit, and referring physicians thereafter. Drug concentration and therapeutic effectiveness will be assessed before (baseline) and 6 months after recommendations have been provided. To assess effectiveness, patient-reported outcomes will be evaluated using validated scales for symptoms of depression, pain and chemotherapy-induced nausea/ vomiting The investigators hypothesize that the pharmacogenetic variation and DDI, if applicable, determine steady state drug concentration and therapeutic response or toxicity of the investigated antidepressant, pain or antiemetic treatments at baseline, while there is a clinically significant reduction or absence of the effect 6 months after the PM clinic recommendations to referring physicians and patients.

Detailed Description
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This prospective longitudinal study will consist of three cohorts of adult cancer patients routinely referred to the PM clinic for genotype-guided chemotherapy including 5-FU or tamoxifen that are also taking antidepressant, analgesic and/or antiemetic medications. Patients will be assigned to one or more cohorts, as appropriate, at the screening visit: Cohort 1 (n=200) if prescribed antidepressants including the selective serotonin reuptake inhibitors (SSRI) citalopram or escitalopram, or the selective norepinephrine reuptake inhibitors (SNRI) venlafaxine or desvenlafaxine; Cohort 2 (n=200) if prescribed opioid pain medications including codeine, oxycodone, hydrocodone, or tramadol; and/or Cohort 3 (N=200) if prescribed the antiemetic agent ondansetron. Each patient will participate in a PM clinic screening visit. Eligible patients will attend three subsequent study visits at 0.5, 4 (virtual), and 7 months after screening. At each PM clinic visit, clinical information and a venous blood sample will be collected. Patients will also complete the ESAS survey and validated scores/ surveys to evaluate treatment effectiveness.

Official Title
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Evaluating the Implementation of Personalized Medicine for Optimal Drug Therapy in Cancer Patients: A Prospective Longitudinal Trial

Conditions
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Nausea With Vomiting Chemotherapy-Induced, Depression, Reactive, Cancer Pain

Intervention / Treatment
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* Genetic: Pharmacogenetic testing
* Other: Drug-Drug interaction analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Prescribed a chemotherapy medication Currently taking one or more study medications (citalopram, escitalopram, venlafaxine, desvenlafaxine, codeine, oxycodone, hydrocodone, tramadol or ondansetron) Exclusion Criteria: Patients who are unable to complete study materials (surveys) with or without assistance, including non-English speaking patients Patients receiving palliative care Patients taking anti-depressants for reason other than depression or anxiety, i.e. hot flash (Only applies to antidepressant cohort) Patients with preexisting major depressive disorder prior to cancer diagnosis (Only applies to antidepressant cohort)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Anti-depressants<br>Patients who have been prescribed either 1) the selective serotonin reuptake inhibitors (SSRI) citalopram or escitalopram, or 2) the selective norepinephrine reuptake inhibitors (SNRI) venlafaxine or desvenlafaxine | Genetic: Pharmacogenetic testing<br>* Genotyping for CYP2D6 and CYP2C19<br>Other: Drug-Drug interaction analysis<br>* Evaluating potential drug interactions with CYP2D6, CYP2C9 and CYP3A4 inhibitors and inducers using the Medical Letter.<br>|
| Opioid pain medications<br>Patients who have been prescribed opioid pain medications including codeine, oxycodone, hydrocodone, or tramadol. | Genetic: Pharmacogenetic testing<br>* Genotyping for CYP2D6 and CYP2C19<br>Other: Drug-Drug interaction analysis<br>* Evaluating potential drug interactions with CYP2D6, CYP2C9 and CYP3A4 inhibitors and inducers using the Medical Letter.<br>|
| Anti-metics<br>Patients who have been prescribed the antiemetic agent ondansetron | Genetic: Pharmacogenetic testing<br>* Genotyping for CYP2D6 and CYP2C19<br>Other: Drug-Drug interaction analysis<br>* Evaluating potential drug interactions with CYP2D6, CYP2C9 and CYP3A4 inhibitors and inducers using the Medical Letter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug level measurements | Steady-state drug plasma concentration of the antidepressant (Cohort 1), pain (Cohort 2) or antiemetic medication (Cohort 3) at follow-up visit 2 at 6 months compared to the baseline visit as assessed by single time points | Baseline visit to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Edmonton Symptom Assessment Scale (ESAS) Survey | Difference in ESAS survey results in each cohort at the follow up visits (3 and 6 months) compared to baseline visit | Baseline visit to 6 months | 
| Center for Epidemiologic Studies Depression Scale (CES-D) Survey | Difference in CES-D survey results in each cohort at the follow up visits (3 and 6 months) compared to baseline visit | Baseline visit to 6 months | 
| Visual Analog Scale (VAS) for pain | Difference in VAS Pain score in each cohort at the follow up visits (3 and 6 months) compared to baseline visit | Baseline visit to 6 months | 
| MASCC Antiemesis Tool (MAT) survey | Difference in MAT survey results in each cohort at the follow up visits (3 and 6 months) compared to baseline visit | Baseline visit to 6 months | 
| Antidepressant Side-Effect Checklist (ASEC) | Difference in ASEC score in each cohort at the follow up visits (3 and 6 months) compared to baseline visit | Baseline visit to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Personalized medicine, Pharmacogenetics, Therapeutic drug monitoring