Efficacy and Safety of Duloxetine in Chinese Solid Tumor Patients With Taxanes-induced Painful Peripheral Neuropathy

Study Overview
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Brief Summary
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The study is to evaluate the efficacy and safety of duloxetine in Chinese solid tumor patients with taxanes-induced painful peripheral neuropathy. Duloxetine will be given to patients who have grade 1 or higher sensory neuropathy according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and at least 4 on a scale of 0 to 10 points, representing average chemotherapy-induced pain, after taxanes treatment. Patient-reported pain severity, functional interference, emotion condition and quality of Life will be assessed weekly using corresponding scales. Blood samples will be collected from each enrolled subjects before the start of treatment, and the potential biomarkers in predicting duloxetine efficacy or safety will be explored by genomic profiling.

Official Title
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A Single-Center, Single-Arm Clinical Trail Evaluating Efficacy and Safety of Duloxetine in Chinese Solid Tumor Patients With Taxanes-induced Painful Peripheral Neuropathy

Conditions
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Chemotherapy-induced Peripheral Neuropathy, Pain, Solid Tumor

Intervention / Treatment
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* Drug: Duloxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must sign an informed consent form (ICF) voluntarily and be able to understand and comply with the requirements of the study; Patients must be 18 to 75 years of age (including cut-offs) on the date of signing the informed consent form, regardless of gender; Patients must be diagnosed with malignant solid tumors by pathological histology or cytology in the central laboratory or study center; Patients must received treatment with a chemotherapy regimen containing taxanes; Patients must have ≥ grade 1 sensory chemotherapy-induced peripheral neuropathy (CIPN) with NRS ≥ 4/10 according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0 grading scale Eastern Cooperative Oncology Group performance status (ECOG PS): 0-2; Expected survival of ≥ 3 months; Screening values at screening meet the following requirements: (no blood components, cell growth factors, leukocyte-lifting drugs, platelet-lifting drugs, anemia-correcting drugs, etc. are allowed within 14 days prior to obtaining laboratory tests); Complete blood count: neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 90 × 109/L, hemoglobin (Hb) ≥ 90 g/L; Liver function: glutamic aminotransferase (AST), alanine aminotransferase (ALT) and total serum bilirubin (TBIL) ≤ 2 times the upper limit of normal range (ULN) Renal function: serum creatinine (Cr) ≤ ULN or creatinine clearance (CCr) ≥ 80 mL/min (applying the standard Cockcroft -Gault formula); Female patients who are non-lactating and must have a negative pregnancy test result; Patients of childbearing potential must agree to use effective contraception for at least 30 days after signing the informed consent to the last dose. Note: Concomitant use of selected analgesics (e.g., opioids, acetaminophen, aspirin, and other NSAIDs) is permitted, but only patients receiving a stable dose during the two weeks prior to enrollment may participate. Exclusion Criteria: Patients with known hypersensitivity to duloxetine or any of the inactive ingredients in the product; Patients on other concomitant medications known to affect 5-hydroxytryptamine (5-HT) levels; Patients who must take monoamine oxidase inhibitors for antidepressant treatment； Patients with the presence of active brain or meningeal metastases； Patients with the presence of uncontrolled closed-angle glaucoma； Patients with the presence of neuropathy caused by any type of nerve compression； The presence of mental illness, epilepsy, mania, suicidal depression, dementia or alcohol or drug abuse that may have an impact on compliance with trial requirements; The presence of comorbid cardiovascular disease, including but not limited to: (1) New York Heart Association (NYHA) criteria ≥ grade 2 heart failure; (2) severe/unstable angina pectoris; (3) myocardial infarction or cerebrovascular accident within 6 months prior to first dose; (4) atrial fibrillation and supraventricular or ventricular arrhythmias requiring treatment; (5) pre-existing symptomatic superior vena cava syndrome; (6) corrected QT interval (QTc) > 450 ms (men); QTc > 470 ms (women); (7) hypertensive disease not controlled by antihypertensive medication: systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg; Patients with other medical history or evidence of disease that has the potential to confound trial results are excluded from the study； Patients are excluded from the study if investigator/sponsor believes that participation in the study is not in the subject's best interest.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Duloxetine treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine arm<br>Chemotherapy regimens consisting of taxanes will be used according to treatment specifications. Subjects require therapeutic intervention for painful peripheral neuropathy will receive duloxetine 20 mg (orally, once daily) as the starting dose for 1 cycle of 7 days; the current dose will be maintained for effective pain control (NRS ≤ 3 points) and increased by 20 mg at the next cycle assessment for ineffective pain control (NRS > 3 points) up to a maximum dose of 60 mg (orally, once daily). Duloxetine administration will be maintained until the uncontrolled pain (under the condition of treatment with duloxetine at its maximum dose), intolerable toxicity, completed antineoplastic therapy or subject loss of visit, death, withdrawal of informed consent, or other conditions occur. The administration of duloxetine is up to a maximum of 12 weeks. | Drug: Duloxetine<br>* Duloxetine, tablets, 20mg as starting dose and up to 60mg as maximum dose, once daily. Taxanes is used according to manual instruction and patient condition.<br>* Other names: Chemotherapy containing taxanes;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Score | Scale title: Brief Pain Inventory Short Form (BPI-SF). Description: Pain severity items are scored using an 11-point numeric rating scale (0, no pain; 10, pain as bad as you can imagine). | Once every 7 days after treatment initiation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Score | Scale title: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) Description: Items in FACT/GOG-Ntx are scored using an 5-point numeric rating scale (0, not at all; 4, very much). | Once every 7 days after treatment initiation. | 
| Function Score | Scale title: Brief Pain Inventory Short Form (BPI-SF). Description: Degree of pain-related functional interference is based on partial items in the BPI-SF and scored using an 11-point numeric rating scale, (0, does not interfere; 10, completely interferes). | Once every 7 days after treatment initiation. | 
| Anxiety and depression Score | Scale 1 title: Hamilton Anxiety Rating Scale (HAM-A) Description: Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Scale 2 title: Hamilton Depression Rating Scale (HDRS17) Description: HDRS17 uses a 5-point scale of 0 to 4 for most items and a 3-point scale of 0 to 2 for a few items, and higher scores mean a worse symptom. The total scores less than 7 or 7 are indicative of the absence of depression or being normal, 8-16 consider mild depression, 17-23 suggest moderate depression and scores 24 or over are indicative of severe depression. | Once every 7 days after treatment initiation. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy-induced Peripheral Neuropathy, Pain, Duloxetine, Taxanes, Solid tumor