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.

Conditions

Eligibility

Eligible Ages
Over 25 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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)

- 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)

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Supportive Care
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase II, Arm I (duloxetine hydrochloride, placebo)
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.
  • Drug: Oxaliplatin
    Given standard of care oxaliplatin
  • Drug: Duloxetine Hydrochloride
    Given PO
  • Drug: Duloxetine
    Given PO
  • Other: Quality-of-Life Assessment
    Ancillary studies
  • Other: Questionnaire Administration
    Ancillary studies
  • Other: Placebo
    Given PO
Experimental
Phase II, Arm II (duloxetine hydrochloride)
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.
  • Drug: Oxaliplatin
    Given standard of care oxaliplatin
  • Drug: Duloxetine Hydrochloride
    Given PO
  • Drug: Duloxetine
    Given PO
  • Other: Quality-of-Life Assessment
    Ancillary studies
  • Other: Questionnaire Administration
    Ancillary studies
Placebo Comparator
Phase II, Arm III (placebo)
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.
  • Drug: Oxaliplatin
    Given standard of care oxaliplatin
  • Other: Quality-of-Life Assessment
    Ancillary studies
  • Other: Questionnaire Administration
    Ancillary studies
  • Other: Placebo
    Given PO
Experimental
Phase III, Arm I (duloxetine hydrochloride)
Patients in Phase III receive most promising dose of duloxetine hydrochloride from Phase II PO QD in the absence of unacceptable toxicity.
  • Drug: Oxaliplatin
    Given standard of care oxaliplatin
  • Drug: Duloxetine Hydrochloride
    Given PO
  • Drug: Duloxetine
    Given PO
  • Other: Quality-of-Life Assessment
    Ancillary studies
  • Other: Questionnaire Administration
    Ancillary studies
Placebo Comparator
Phase III, Arm II (placebo)
Patients in Phase III receive placebo PO QD in the absence of unacceptable toxicity.
  • Drug: Oxaliplatin
    Given standard of care oxaliplatin
  • Other: Quality-of-Life Assessment
    Ancillary studies
  • Other: Questionnaire Administration
    Ancillary studies
  • Other: Placebo
    Given PO

Recruiting Locations

University of Kansas Health System Saint Francis Campus
Topeka, Kansas 66606
Contact:
Site Public Contact
785-295-8000

More Details

Status
Recruiting
Sponsor
Alliance for Clinical Trials in Oncology

Study Contact

Ellen M. Lavoie Smith, PhD
734-936-1267
ellenls@med.umich.edu

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.