Summary

Eligibility
for people ages 25 years and up (full criteria)
Location
at Sacramento, California and other locations
Dates
study started
estimated completion

Description

Summary

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.

Official Title

Duloxetine to Prevent Oxaliplatin-Induced Chemotherapy-Induced Peripheral Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase II to Phase III Study

Details

The primary and secondary objectives of the study: 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.

Keywords

Stage II Colorectal Cancer AJCC v8 Stage III Colorectal Cancer AJCC v8 Colorectal Neoplasms Peripheral Nervous System Diseases Oxaliplatin Duloxetine Hydrochloride Duloxetine Quality-of-Life Assessment

Eligibility

For people ages 25 years and up

  • Stage II-III colorectal cancer patients scheduled to receive oxaliplatin 510 mg/m2 (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/m2 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/m2 every 3 weeks for 12 weeks (i.e., 4 cycles)

  • No prior neurotoxic chemotherapy
  • No pre-existing clinical or pre-clinical peripheral neuropathy from any cause.
  • No history of seizure disorder,
  • No history of narrow-angle glaucoma.
  • No symptoms of or history of schizophrenia, bipolar disease, suicidal thoughts and/or a major depression.
  • No serious eating disorder such as bulimia or anorexia.
  • No known diagnosis of ethanol (ETOH) addiction/dependence within the past 10 years.
  • 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 anticipated or concurrent use of any antidepressant or serotonin-altering agent known to interact with duloxetine, due to concern regarding cumulative toxicity and potential drug interactions.
  • Use of a monoamine oxidase inhibitor (MAOI) or other antidepressants must be discontinued at least 14 days prior to start of protocol treatment.
  • No concomitant treatment with strong CYP1A2 and CYP2D6 inhibitors.
  • 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.
  • No use of warfarin or heparin products.
  • 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
  • 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)

Locations

  • University of California Davis Comprehensive Cancer Center accepting new patients
    Sacramento California 95817 United States
  • Providence Queen of The Valley accepting new patients
    Napa California 94558 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Alliance for Clinical Trials in Oncology
Links
Sign up for this study
ID
NCT04137107
Phase
Phase 2/3 research study
Study Type
Interventional
Participants
Expecting 327 study participants
Last Updated