GA NCORP

NCORP Trials

Duloxetine to Prevent Oxaliplatin-Induced Peripheral Neuropathy

Status
Active
Cancer Type
Colon/Rectal Cancer
Unknown Primary
Trial Phase
Phase II
Phase III
Eligibility
25 Years and older, Male and Female
Study Type
Supportive care
NCD ID
NCT04137107
Protocol IDs
A221805 (primary)
A221805
A221805
NCI-2019-04727
Study Sponsor
Alliance for Clinical Trials in Oncology

Summary

This phase II/III trial studies the best dose of duloxetine and how well it works in preventing pain, tingling, numbness, and muscle weakness (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.

Objectives

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)
IV. Compare ePRO uptake in patients who do and do not have access to electronic patient-reported outcome (ePRO)-E. (Correlative study)

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 (QLQ)-Chemotherapy-Induced Peripheral Neuropathy (CIPN)20 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 (BPI)-Short Form (SF) patient-reported the average and worse 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. (Phase III)
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)
V. Compare ePRO data submission patterns in patients who do and do not have access to ePRO-E. (Correlative study)

EXPLORATORY OBJECTIVES:
I. To explore differences in the response profile by arm of the patient-reported outcomes obtained from the QLQ-CIPN20, BPI-SF, including the BPI-SF interference subscale, and the 7-day average of chronic (worse and average) neuropathic pain obtained from the 7-day chronic neuropathy pain diary, measured longitudinally over the entire study period. (Phase III)
II. To explore between-arm differences in the time to initial onset of sensory OIPN (numbness [N], tingling [T], and pain). (Phase III)
III. To explore between-arm differences in the pattern of acute, more transient neuropathy symptoms reported with oxaliplatin therapy. (Phase III)
IV. To explore between-arm differences in the percentages of patients receiving full planned oxaliplatin doses per cycle. (Phase III)
V. To characterize the frequency and severity of patient-reported pain, numbness, and tingling as measured by the Patient Reported Outcomes (PRO)-CTCAE. (Phase III)
VI. To document the reasons why a patient chose not to use the electronic patient-reported outcome (ePRO) tool to complete the study questionnaires. (Phase III)
VII. Using a quantitative and qualitative data collection methods, describe the demographic and clinical characteristics, and technology attitudes and experiences of all A221805 participants (control and intervention group patients) who do and do not elect to use ePRO as their preferred method for submitting PRO study questionnaires. (Correlative study)

OUTLINE:
PHASE II: Patients are randomized to 1 of 3 arms.

Patients in Phase II receive duloxetine hydrochloride orally (PO) once daily (QD) during week 1, duloxetine hydrochloride PO QD and placebo PO QD during weeks 2-16, followed by duloxetine hydrochloride PO QD during week 17 in the absence of unacceptable toxicity.

Patients in Phase II receive duloxetine hydrochloride PO QD during weeks 1-17 in the absence of unacceptable toxicity.

Patients in Phase II receive placebo PO QD during weeks 1-17 in the absence of unacceptable toxicity.

CORRELATIVE STUDY: All patients complete survey at baseline and 21 days and access ePRO.

PHASE III: Patients are randomized to 1 of 2 arms.

Patients in Phase III receive most promising dose of duloxetine hydrochloride from Phase II PO QD during weeks 1-17 in the absence of unacceptable toxicity.

Patients in Phase III receive placebo PO QD during weeks 1-17 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.