A Study to Investigate Nicotinic Acid on VEGFR Inhibitor-Associated Hand-Foot Skin Reactions

Study Overview
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Brief Summary
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Hand-Foot Skin Reaction (HFSR) is a common adverse event induced by Vascular Endothelial Growth Receptor Inhibitor (VEGFRi) in cancer patients. The main purpose of this study is to evaluate the efficacy and safety of nicotinic acid in solid tumor patients with grade II/III VEGFRi-associated HFSR.

Official Title
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Efficacy of Nicotinic Acid for VEGFR Inhibitor-Associated Hand-Foot Skin Reactions in Solid Tumor Patients: a Randomised Controlled Phase 2 Trial

Conditions
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Hand-Foot Skin Reaction (HFSR)

Intervention / Treatment
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* Drug: Nicotinic acid +Routine care
* Drug: Routine care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained prior to performing any protocol-related procedures, including blood serum collecting HFSR grade 2 or higher after treatment with VEGFR inhibitors (such as sorafenib, regorafenib, anlotinib, and apatinib), according to NCI CTCAE V5.0 - PPE Age from 18 to 75 years. Life expectancy of at least 3 months at Day 1 Exclusion Criteria: History of allergy to B vitamins Major surgery or severe traumatic injury, fracture within 4 weeks prior to first dose of nicotinic acid or ulceration and any factors that significantly affect oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction Patient who takes isoniazid in combination with sorafenib and other VEGFR inhibitors. History of psychiatric drugs substance abuse and fails to quit it or has amental disorder Pregnant or nursing women, fertile patient who is unwilling or unable to use effective contraception

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotinic acid + Routine care<br>Nicotinic acid is administered orally at 50 mg (grade 2) or 100 mg (grade 3) three times daily with routine care. | Drug: Nicotinic acid +Routine care<br>* Nicotinic acid is administered orally at 50 mg (grade 2) or 100 mg (grade 3) three times daily with routine care.<br>* Other names: Nicotinic Acid 50 MG Oral Tablet;|
| Active Comparator: Routine care<br>Routinely apply urea ointment and provide best supportive care. | Drug: Routine care<br>* Routinely apply urea ointment and provide best supportive care.<br>* Other names: Urea ointment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate of VEGFR inhibitor-associated hand-foot skin reaction | Proportion of patients who achieve NCI CTCAE v5.0 - Palmar-Plantar Erythrodysesthesia (PPE) grade 0/1 (enrolled grade 2 patients) or grade 0-2 (enrolled grade 3 patients). | 2 year | 
| Complete response rate of VEGFR inhibitor-associated hand-foot skin reaction | Proportion of patients who achieve NCI CTCAE v5.0 - PPE grade 0. | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose adjustment/withdrawal ratio | Proportion of patients who need dose adjustment or withdrawal of VEGFR inhibitors, such as sorafenib, regorafenib, anlotinib, and apatinib. | 2 year | 
| Hand-Foot Reaction Quality of Life (HF-QoL) | Hand-Foot Reaction Quality of Life (HF-QoL) questionnaire, scoring results statistics. The HF-QoL symptom and daily activity total scores were transformed to a scale of 0 to 4, based on the sum of each unit-weighted item score divided by the maximum score. Higher scores on the HF-QoL indicate worse quality of life or greatersymptom burden. | 2 year |