IRB Study Number A221805
Status Recruiting
Institute Taussig Cancer Institute
Description
2.1 Primary objectives
2.1.1 Phase II Primary Objective:
a. To determine the dosage of duloxetine (30 mg or 60 mg daily) that appears most promising in preventing OIPN, as assessed on Day 1 of each oxaliplatin treatment cycle as well as 2 weeks (14 days) after day 1/cycle 4 (CAPOX) or day 1/cycle 6 (FOLFOX), regardless of the oxaliplatin treatment regimen received (3- or 6- month FOLFOX or 3-month CAPOX).
2.1.2 Phase III Primary Objective:
a. To demonstrate that the most promising dosage of duloxetine identified in the Phase II component is more effective than placebo at preventing OIPN sensory symptoms, as assessed on Day 1 of each oxaliplatin treatment cycle as well as 2 weeks (14 days) after day 1/cycle 4 (CAPOX) or day 1/cycle 6 (FOLFOX), regardless of the oxaliplatin treatment regimen received (3-or 6-month FOLFOX or 3-month CAPOX).
2.2 Secondary objectives
2.2.1 Phase II Secondary Objective:
a. To characterize toxicity in each arm, including duloxetine side effects of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia using CTCAE v 5.0 as well as characterizing the toxicity profile within the two distinct patient cohorts: those receiving 3- or 6-month oxaliplatin regimens.
2.2.2 Phase III Secondary Objectives:
a. To compare the serially measured OIPN total sensory neuropathy scores calculated from the six individual QLQ-CIPN20 questions that quantify numbness, tingling, and pain in the fingers (or hands) and toes (or feet), assessed on Day 1 of each oxaliplatin treatment cycle as well as 2 weeks (14 days) after day 1/cycle 4 (CAPOX) or day 1/cycle 6 (FOLFOX) regardless of oxaliplatin treatment regimen received (3- or 6-month FOLFOX or 3-month CAPOX) between the most promising dosage of duloxetine identified in the Phase II component and placebo.
b. To characterize toxicity in each arm, including duloxetine side effects of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia using the CTCAE v 5.0 as well as characterizing the toxicity profile within the two distinct patient cohorts: those receiving 3- or 6-month oxaliplatin regimens.
Inclusion Criteria
3.2.1 Stage II-III colorectal cancer patients scheduled to receive oxaliplatin via one of the following treatment regimens:
• FOLFOX (3-month): 510 mg/m2 (total planned maximum cumulative dose) over 12 weeks (6 cycles), in which patients are scheduled to receive oxaliplatin 85 mg/m2 every 2 weeks.
• FOLFOX (6-month): 1020 mg/m2 (total planned maximum cumulative dose) over 24 weeks (12 cycles) in which patients are scheduled to receive oxaliplatin 85 mg/m2 every 2 weeks.
• CAPOX (3-month): 520 mg/m2 (total planned maximum cumulative dose) over 12 weeks (4 cycles) in which patients are scheduled to receive oxaliplatin 130 mg/m2 every 3 weeks.
3.2.2 No prior neurotoxic chemotherapy.
3.2.3 No pre-existing clinical or pre-clinical peripheral neuropathy from any cause.
3.2.4 Comorbid conditions: Patients with the following comorbid conditions are not eligible:
• History of seizure disorder
• Narrow-angle glaucoma
• History of suicidal thoughts
• Symptoms of or a history of schizophrenia, bipolar disease, and/or a major depression
• A serious eating disorder such as bulimia or anorexia
• Known diagnosis of ethanol (ETOH) addiction/dependence within the past 10 years
3.2.5 Concomitant medications:
• No concomitant use of other adjuvant pharmacologic interventions (e.g., gabapentin, pregabalin, venlafaxine) with known or hypothesized efficacy for peripheral neuropathy. Must be discontinued at least 7 days prior to start of protocol treatment.
• No concomitant use of non-pharmacologic interventions (known or hypothesized) for CIPN (e.g., cryotherapy, acupuncture).
• No anticipated or concurrent use of warfarin or heparin products while patients are receiving study drug. No anticipated or concurrent use of any antidepressant or serotonin-altering agent or other potent CYP2D6 inhibitors (e.g. paroxetine, fluoxetine, quinidine) known to interact with duloxetine, due to concern regarding cumulative toxicity and potential drug interactions. Use of an MAOI or other antidepressants must be discontinued at least 14 days prior to start of protocol treatment.
• Chronic concomitant treatment with drugs that are extensively metabolized by CYP2D6 and that have a narrow therapeutic index, including certain antidepressants, phenothiazines, and Type 1C antiarrhythmics should be approached with caution.
• Concomitant administration of duloxetine and thioridazine should be avoided.
• Chronic concomitant treatment with strong CYP1A2 inhibitors should be avoided during this trial due to concern regarding cumulative toxicity and potential drug interactions.
3.2.6 Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
Therefore, for women of childbearing potential, a negative pregnancy test done ≤ 7 days prior to registration is required.
3.2.7 Age ≥ 25 years. Duloxetine black box warnings indicate an increased risk of suicide in patients < 25 years of age.
3.2.8 ECOG Performance Status 0-2
3.2.9 Language: In order to complete the mandatory patient-completed measure, patients must be able to speak and read English.
3.2.10 Required Initial Laboratory Values:
Calc. Creatinine Clearance > 30 mL/min
AST/ SGOT ≤ 3 x upper limit of normal (ULN)
Exclusion Criteria
Exclusion Criteria Not Available
