High Dose Inorganic Selenium for Preventing Chemotherapy Induced Peripheral Neuropathy

Phase 3UnknownNCT04201561

Seoul National University Hospital68 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

Interventions

sodium selenite pentahydrateDRUG

High-dose inorganic selenium (2000 μg/40 ml) will be administered before chemotherapy in patients assigned to the experimental group.

Normal salineDRUG

Normal saline (40 ml) will be administered before chemotherapy in patients assigned to the control group.

ChemotherapyDRUG

Paclitaxel (175mg/m2), carboplatin (AUC 5.0 or 6.0) IV, and bevacizumab IV (15mg/kg) D1, every three weeks.

Eligibility

Sex: FEMALEMin age: 19 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Informed consent 2. Age: 19-80 years old 3. 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. 4. Patients who have received paclitaxel chemotherapy for a minimum of 6 cycles and a maximum of 9 cycles 5. Eastern Cooperative Oncology Group performance status 0-2 6. Patients with no other concurrent disease affecting overall survival 7. Patients with normal hematologic, renal, and liver functions 8. Patients who understand the contents of the clinical trial and are capable of participating until the end of the trial Exclusion Criteria: 1. Pregnancy or breastfeeding 2. Patients diagnosed with recurrent ovarian cancer, fallopian cancer, or primary peritoneal cancer who received secondary debulking surgery. 3. Patients diagnosed with recurrent ovarian cancer, fallopian cancer, or primary peritoneal cancer who did not receive Bevacizumab chemotherapy 4. Patients with other concurrent disease that can affect overall survival (infection, hypertension, diabetes, cardiac disease, etcetera) 5. Patients with underlying disease (diabetes, neuropathy, brain or bone metastasis) that can induced neuropathy 6. Patients allergic to selenium 7. Inappropriate patients by the researcher's decision

Outcomes

Primary Outcomes

Incidence of chemotherapy-induced peripheral neuropathy (3m)

To evaluate the incidence of CIPN by evaluating paresthesia, pain and motor based on WHO-CIPN criteria.

Time frame: Examined at 3 months after last paclitaxel chemotherapy

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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

Time frame: 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

concomitant medication1

Dosage and usage of concomitant medication (neurontin) for CIPN

Time frame: 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

Time frame: 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

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

Time frame: 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

Time frame: 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