High Dose Inorganic Selenium for Preventing Chemotherapy Induced Peripheral Neuropathy

Study Overview
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Brief Summary
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This study aims to evaluate the safety and efficacy of high dose inorganic selenium in preventing and relieving chemotherapy-induced peripheral neuropathy (CIPN) in platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer patients. This study will be conducted as a phase III randomized controlled trial in platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer patients who are expected to undergo paclitaxel-carboplatin chemotherapy. A total of 68 patients need to be enrolled in this study. The primary objective of this study is to evaluate the frequency of chemotherapy-induced peripheral neuropathy. The secondary objectives are the evaluation of the severity of peripheral neuropathy and the quality of life to show that selenium is effective in preventing and relieving peripheral neuropathy induced by paclitaxel. Positive results in this study will lead to further studies investigating the effect of selenium on other chemotherapies that can induce peripheral neuropathy.

Detailed Description
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High-dose selenium is known to reduce systemic inflammatory responses through antioxidant and anti-inflammatory effects. Selenium has also been shown in pre-clinical studies to inhibit chemotherapy-induced peripheral neuropathy through reactive oxygen species mechanisms in cells. Therefore, the investigators aimed to confirm the effect of preventing high dose intravenous selenium prior to chemotherapy and to prevent neuropathy caused by chemotherapy. In this study, the investigators will identify the frequency and severity of CIPN according to World Health Organization (WHO) criteria. Also, the investigators will assess the patient's quality of life (QoL), evaluate the effects of the administration of inorganic selenium on CIPN and QoL, and confirm the safety of high-dose selenium. I would like to.

Official Title
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Safety and Efficacy of High Dose Inorganic seLenium for Preventing Chemotherapy Induced pEripheral Neuropathy in platINUM Sensitive Recurrent Ovarian, Fallopian, Primary Peritoneal Cancer: Phase III Randomised Controlled Trial

Conditions
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Chemotherapy-induced Peripheral Neuropathy, Recurrent Ovarian Carcinoma, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma

Intervention / Treatment
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* Drug: sodium selenite pentahydrate
* Drug: Normal saline
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Age: 19-80 years old Complete or partial response according to Response Evaluation Criteria In Solid Tumors (RECIST) or Gynecologic Cancer Intergroup criteria in epithelial ovarian cancer, fallopian cancer, or primary peritoneal cancer patients who underwent either surgery or chemotherapy and those who have recurred cancer at least six months after chemotherapy. Patients who have received paclitaxel chemotherapy for a minimum of 6 cycles and a maximum of 9 cycles Eastern Cooperative Oncology Group performance status 0-2 Patients with no other concurrent disease affecting overall survival Patients with normal hematologic, renal, and liver functions Patients who understand the contents of the clinical trial and are capable of participating until the end of the trial Exclusion Criteria: Pregnancy or breastfeeding Patients diagnosed with recurrent ovarian cancer, fallopian cancer, or primary peritoneal cancer who received secondary debulking surgery. Patients diagnosed with recurrent ovarian cancer, fallopian cancer, or primary peritoneal cancer who did not receive Bevacizumab chemotherapy Patients with other concurrent disease that can affect overall survival (infection, hypertension, diabetes, cardiac disease, etcetera) Patients with underlying disease (diabetes, neuropathy, brain or bone metastasis) that can induced neuropathy Patients allergic to selenium Inappropriate patients by the researcher's decision

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients enrolled in this study will be randomized into two groups. Patients in the control group will receive paclitaxel chemotherapy every 3 weeks for a total of 6 cycles and a dose of normal saline 40 ml every cycle before chemotherapy begins. Patients in the experimental group will receive a dose of selenium 2000 μg/40 ml instead every cycle before chemotherapy.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>The patient will receive an intravenous selenium 2000 μg/40 ml dose just before chemotherapy begins every cycle (every 3 weeks for 6 cycles). Afterward, the same dose will be continued during the maintenance period if it is medically required or if the patient desires to do so. | Drug: sodium selenite pentahydrate<br>* High-dose inorganic selenium (2000 μg/40 ml) will be administered before chemotherapy in patients assigned to the experimental group.<br>* Other names: Selentab inj. A12CE02;Drug: Chemotherapy<br>* Paclitaxel (175mg/m2), carboplatin (AUC 5.0 or 6.0) IV, and bevacizumab IV (15mg/kg) D1, every three weeks.<br>* Other names: Paclitaxel, carboplatin and bevacizumab;|
| Placebo Comparator: Placebo group<br>The patient will receive an intravenous normal saline 40 ml dose just before chemotherapy begins every cycle (every 3 weeks for 6 cycles). Afterward, the same dose will be continued during the maintenance period if it is medically required or if the patient desires to do so. | Drug: Normal saline<br>* Normal saline (40 ml) will be administered before chemotherapy in patients assigned to the control group.<br>* Other names: sodium chloride 0.9%;Drug: Chemotherapy<br>* Paclitaxel (175mg/m2), carboplatin (AUC 5.0 or 6.0) IV, and bevacizumab IV (15mg/kg) D1, every three weeks.<br>* Other names: Paclitaxel, carboplatin and bevacizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of chemotherapy-induced peripheral neuropathy (3m) | To evaluate the incidence of CIPN by evaluating paresthesia, pain and motor based on WHO-CIPN criteria. | Examined at 3 months after last paclitaxel chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of chemotherapy-induced peripheral neuropathy (baseline, 3wk) | To evaluate the incidence of CIPN by evaluating paresthesia, pain and motor based on WHO-CIPN criteria. | Examined on the day 0 of first chemotherapy, 3 weeks after last paclitaxel chemotherapy, and checked before start of every chemotherapy cycles (each cycle is 21 days) | 
| Severity of chemotherapy-induced peripheral neuropathy | To evaluate the severity of CIPN by evaluating paresthesia, pain and motor based on WHO-CIPN criteria. | Examined on the day 0 of first chemotherapy, 3 weeks after last paclitaxel chemotherapy, 3 months after last paclitaxel chemotherapy, and checked before start of every chemotherapy cycles (each cycle is 21 days) | 
| Assessment of quality of life1 | Scoring of quality of life assessment using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scale: 30-126, the higher score means better quality of life | Examined on the day 0 of first chemotherapy, 3 weeks after completion of 3 cycles of chemotherapy, 3 weeks after completion of 6 cycles of chemotherapy, and 3 months after completion of 6 cycles of chemotherapy (each cycle is 21 days) | 
| Assessment of quality of life2 | Scoring of quality of life assessment using European Organization for Research and Treatment of Cancer Chemotherapy Induced Peripheral Neuropathy 20 (EORTC-CIPN20) Scale: 20-80, the higher score mean worse symptom | Examined on the day 0 of first chemotherapy, 3 weeks after completion of 3 cycles of chemotherapy, 3 weeks after completion of 6 cycles of chemotherapy, and 3 months after completion of 6 cycles of chemotherapy (each cycle is 21 days) | 
| concomitant medication1 | Dosage and usage of concomitant medication (neurontin) for CIPN | Checked on the day 0 of every cycles of chemotherapy, 3 weeks after completion of 3 cycles of chemotherapy, 3 weeks after completion of 6 cycles of chemotherapy, and 3 months after completion of 6 cycles of chemotherapy (each cycle is 21 days) | 
| concomitant medication2 | Dosage and usage of concomitant medication (duloxetine) for CIPN | Checked on the day 0 of every cycles of chemotherapy (each cycle is 21 days), from day 1 to day 21 on each cycle | 
| concomitant medication3 | Dosage and usage of concomitant medication (celecoxib) for CIPN | Checked on the day 0 of every cycles of chemotherapy, 3 weeks after completion of 3 cycles of chemotherapy, 3 weeks after completion of 6 cycles of chemotherapy, and 3 months after completion of 6 cycles of chemotherapy (each cycle is 21 days) | 
| Adverse events 1 | Evaluation of chemotherapy-induced toxicity hematologic (ANC, Hb, Plt) and non-hematologic (nausea, vomiting, diarrhea, constipation, hypersensitivity reaction) symptoms are evaluated by Common Terminology Criteria for Adverse Events ver 5.0 by grade | From the day 1 of chemotherapy to the day before starting next cycle (each cycle is 21 days), 3 weeks after completion of 3 cycles of chemotherapy, 3 weeks after completion of 6 cycles of chemotherapy, and 3 months after completion of 6 cycle | 
| Adverse events 2 | Evaluation of any toxicity related to intravenous selenium administration (garlic odor, nausea, vomiting, hypersensitivity reaction) symptoms are evaluated by Common Terminology Criteria for Adverse Events ver 5.0 by grade | From the date of first day of chemotherapy to the day before starting next cycle (each cycle is 21 days), 3 weeks after completion of 3 cycles of chemotherapy, 3 weeks after completion of 6 cycles of chemotherapy, and 3 months after completion of 6 cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral neuropathy, recurrent ovarian cancer, high-dose inorganic selenium, sodium selenite