Efficacy of Metformin as Preventive Treatment in Paclitaxel Induced Peripheral Neuropathy in Breast Cancer Patients

Study Overview
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Brief Summary
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At present, there are no FDA-approved treatments for chemotherapy-induced neuropathy. Discrete neuro anti-inflammatory effects of metformin support its repurposing as a neuroprotective agent in patients with neurodegenerative diseases. Therefore, this study aims to evaluate the effect of metformin on the amelioration of paclitaxel induced neuropathy in cancer patients.

Official Title
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Efficacy of Metformin as Preventive Treatment in Paclitaxel Induced Peripheral Neuropathy in Breast Cancer Patients

Conditions
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Peripheral Neuropathy, Breast Cancer

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (>18 years old) Early-stage breast cancer patients who will receive adjuvant paclitaxel Performance status according to Eastern Cooperative oncology group (ECOG) < 2. Adequate bone marrow function (white blood count ≥4,000/mm3, platelet count ≥100,000/mm3), liver function (serum total bilirubin <1.5 mg/dl), renal function (creatinine<1.5 mg/dl). Exclusion Criteria: Clinical neuropathy at prior to enrollment. Patients treated with medications that increase the risk of neuropathy like amiodarone, Colchicine, metronidazole, phenytoin. Patients with a history of hypersensitivity to metformin. Pregnant or lactating females. Patients who are using metformin for any other cause. Patients with Diabetes mellitus. Receiving vitamin B1, B6, B12 or another vitamin supplemental therapy. Receiving antidepressants, opioids, adjuvant analgesic agents (eg, anticonvulsants, clonazepam, or mexiletine), topical analgesics, and amifostine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (metformin group)<br>who will receive adjuvant paclitaxel in addition to metformin tablets (1700 mg daily) during the chemotherapy treatment duration. | Drug: Metformin<br>* cidophage 850 gm twice daily<br>|
| Placebo Comparator: Group II (control group)<br>who will receive adjuvant weekly paclitaxel. | Drug: Placebo<br>* placebo twice daily for treatment period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of grade II or more peripheral neuropathy at the end of paclitaxel treatment | Grading of paclitaxel induced peripheral neuropathy will be done using NCI-CTCAE version (4.03) | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to develop grade 2or 3 PIPN | The time from randomization till development of grade II or III PN will be recorded for all patients included in the study. | 8 weeks | 
| the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity(FACT-GOG-NTX) subscale | Patient's QOL will be assessed using the validated Arabic version of FACT-GOG-NTX subscale | 8 weeks | 
| Pain Severity | The severity of neuropathic pain will be assessed using the Arabic version of the Brief Pain Inventory Short Form (BPI-SF) | 8 weeks | 
| Serum biomarkers level in (ng/mL) | Nerve growth factor Biomarkers levels will be measured using commercial ELISA kits. | 8 weeks |