Current Clinical Trials

Duloxetine to Prevent Oxaliplatin-Induced Peripheral Neuropathy in Patients With Stage II-III Colorectal Cancer
  1. Henry Tsai, MD
    Henry Tsai, MD
  2. for people 25 Years and up (full criteria)
  3. Rancho Mirage, CA
  4. study started January 2023
  5. Henry Tsai, MD
  6. Accepting new patients

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

A221805-Duloxetine to Prevent Oxaliplatin-Induced Chemotherapy-Induced Peripheral Neuropathy in Patients With Stage II-III Colorectal Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II to Phase III Study

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 ... more
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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

Eligibility

for people 25 Years and up
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... more
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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)

Lead Scientists at Eisenhower Health

Henry Tsai, MD
For Henry Tung-Yun Tsai, MD, MA, a Board Certified Hematologist and Medical Oncologist – specializing in the treatment colon cancer and other gastrointestinal cancers, medicine has always been a part of his life. Originally from Taiwan, Dr. Tsai’s father and sisters all have careers in medicine – ranging in specialties from pharmacy to general surgery.  After having moved from Taiwan at age 14, Dr. Tsai attended the University of Calif... more
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For Henry Tung-Yun Tsai, MD, MA, a Board Certified Hematologist and Medical Oncologist – specializing in the treatment colon cancer and other gastrointestinal cancers, medicine has always been a part of his life. Originally from Taiwan, Dr. Tsai’s father and sisters all have careers in medicine – ranging in specialties from pharmacy to general surgery. 

After having moved from Taiwan at age 14, Dr. Tsai attended the University of California at Berkeley where he received his Bachelor of Arts in molecular and cell biology/neurobiology. He received a Master of Arts degree in medical sciences from Boston University and attended medical school at Wayne State University School of Medicine in Detroit, Michigan.

Upon graduating from medical school, he moved to Atlanta, Georgia for an internship, residency and a fellowship in Hematology/Oncology at Emory University. It was at Emory where Dr. Tsai grew to love his chosen specialty: cancer care.

“Yes, cancer care is one of the most difficult fields to practice,” says Dr. Tsai. “But, it is also the most stimulating and rewarding. There are days when I see my patients get better and I have experienced hope. I feel privileged to be a part of their process.”

Dr. Tsai has been a member of the American Medical Association, American College of Physicians, American Society of Clinical Oncology. He has been the local principle investigator for various clinical trials and has presented at workshops and symposiums across the United States. He has authored a book chapter and manuscript related to cancer.

Clinical Study Details

  1. Accepting new patients
  2. study started January 2023
  3. Interventional
  4. April 04, 2024