Official Title
Duloxetine to Prevent Oxaliplatin-Induced Chemotherapy-Induced Peripheral Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase II to Phase III Study
Purpose
This phase II/III trial studies the best dose of duloxetine and how well it works in preventing pain, tingling, and numbness (peripheral neuropathy) caused by treatment with oxaliplatin in patients with stage II-III colorectal cancer. Duloxetine increases the amount of certain chemicals in the brain that help relieve depression and pain. Giving duloxetine in patients undergoing treatment with oxaliplatin for colorectal cancer may help prevent peripheral neuropathy.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the dosage of duloxetine hydrochloride (duloxetine) (30 mg or 60 mg daily) that appears most promising in preventing oxaliplatin-induced peripheral neuropathy (OIPN). (Phase II)
II. 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. (Phase III)
III. To demonstrate that the most promising dosage of duloxetine identified in the Phase II component is more effective than placebo at preventing oxaliplatin-induced chronic neuropathic pain. (Phase III)
SECONDARY OBJECTIVES:
I. To characterize toxicity in each arm, including duloxetine side effects of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. (Phase II)
II. To compare the serially measured OIPN total sensory neuropathy scores calculated from the six individual Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness, tingling, and pain in the fingers (or hands) and toes (or feet), measured on day 1 of each cycle of oxaliplatin treatment and at 1 month post-oxaliplatin treatment between the most promising dosage of duloxetine identified in the Phase II component and placebo. (Phase III)
III. To compare the serially measured Brief Pain Inventory Short Form (BPI-SF) patient-reported on the average pain scores, measured on day 1 of each cycle of oxaliplatin treatment and at 1 month post-oxaliplatin treatment between the most promising dosage of duloxetine identified in the Phase II component and placebo.
IV. 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. (Phase III)
OUTLINE:
PHASE II: Patients are randomized to 1 of 3 arms.
ARM I: Patients in Phase II receive duloxetine hydrochloride 30 mg (1 duloxetine capsule) orally (PO) once daily (QD) during week 1, duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD and placebo (1 placebo capsule) PO QD during weeks 2-16, followed by duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD during week 17 in the absence of unacceptable toxicity.
ARM II: Patients in Phase II receive duloxetine hydrochloride 30 mg (1 duloxetine capsule) orally (PO) once daily (QD) during week 1, duloxetine hydrochloride 60 mg (2 duloxetine capsules) PO QD during weeks 2-16, followed by duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD during week 17 in the absence of unacceptable toxicity.
ARM III: Patients in Phase II receive placebo (1 placebo capsule) orally (PO) once daily (QD) during week 1, placebo (2 placebo capsules) PO QD weeks 2-16, followed by placebo (1 placebo capsule) PO QD during week 17 in the absence of unacceptable toxicity.
PHASE III: Patients are randomized to 1 of 2 arms.
ARM I: Patients in Phase III receive most promising dose of duloxetine hydrochloride from Phase II PO QD in the absence of unacceptable toxicity.
ARM II: Patients in Phase III receive placebo PO QD in the absence of unacceptable toxicity.
NOTE: Patients in all arms receive standard of care oxaliplatin during weeks 1-12.
After completion of study, patients are followed up at 30 days and at 3, 6, 12, and 18 months after last oxaliplatin treatment.
Age Limit
25 years & older
Eligibility Criteria
Inclusion Criteria
|
Stage II-III colorectal cancer patients scheduled to receive oxaliplatin 510 mg/m^2 (cumulative dose) over 12 weeks as a component of adjuvant leucovorin calcium (calcium folinate), 5-fluorouracil and oxaliplatin (FOLFOX) treatment, in which patients are scheduled to receive oxaliplatin 85 mg/m^2 every 2 weeks for 12 weeks (i.e., 6 cycles), or adjuvant capecitabine and oxaliplatin (CAPOX) treatment, in which patients are scheduled to receive oxaliplatin 135 mg/m^2 every 3 weeks for 12 weeks (i.e., 4 cycles)
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
In order to complete the mandatory patient-completed measure, patients must be able to speak and read English
Calculated creatinine clearance > 30 mL/min
Aspartate aminotransferases (AST)/serum glutamic-oxaloacetic transaminase (SGOT) =< 3 x upper limit of normal (ULN)
Please contact study team for additional inclusion criteria
|
Exclusion Criteria
|
Please contact study team for exclusion criteria
|
Keywords and/or Specific Medical Conditions
|
|
|
|
|
|
|
|
|
|
-
Digestive System Diseases
|
-
Digestive System Neoplasms
|
|
|
|
|
-
Gastrointestinal Diseases
|
-
Gastrointestinal Neoplasms
|
|
|
|
|
-
Membrane Transport Modulators
|
-
Molecular Mechanisms of Pharmacological Action
|
|
|
|
|
|
|
|
|
|
|
-
Neurotransmitter Uptake Inhibitors
|
|
|
-
Peripheral Nervous System Agents
|
-
Peripheral Nervous System Diseases
|
-
Physiological Effects of Drugs
|
|
|
|
|
|
|
-
Serotonin and Noradrenaline Reuptake Inhibitors
|
|
|
Sponsors
- Alliance for Clinical Trials in Oncology
|
- National Cancer Institute (NCI)
|