High Dose Inorganic Selenium for Preventing Chemotherapy Induced Peripheral Neuropathy

NCT04201561 | Unknown Phase 3 DMC

• 1 other identifier: SELENIUM trial
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

peripheral neuropathy; recurrent ovarian cancer; high-dose inorganic selenium; sodium selenite

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Incidence of chemotherapy-induced peripheral neuropathy (baseline, 3wk)

  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

  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

  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

  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

  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)

Study Arms (2)

Experimental group

EXPERIMENTAL

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; Drug: Chemotherapy

Placebo group

PLACEBO COMPARATOR

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; Drug: Chemotherapy

Interventions

sodium selenite pentahydrate DRUG

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

Also known as: Selentab inj. A12CE02

Experimental group

Normal saline DRUG

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

Also known as: sodium chloride 0.9%

Placebo group

Chemotherapy DRUG

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

Also known as: Paclitaxel, carboplatin and bevacizumab

Experimental group; Placebo group

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Boryung Pharmaceutical Co., Ltd: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Related Publications (13)

• Hay CM, Courtney-Brooks M, Lefkowits C, Hagan TL, Edwards RP, Donovan HS. Symptom management in women with recurrent ovarian cancer: Do patients and clinicians agree on what symptoms are most important? Gynecol Oncol. 2016 Nov;143(2):367-370. doi: 10.1016/j.ygyno.2016.08.235. Epub 2016 Aug 13.

  PMID: 27531571 BACKGROUND

• Hausheer FH, Schilsky RL, Bain S, Berghorn EJ, Lieberman F. Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy. Semin Oncol. 2006 Feb;33(1):15-49. doi: 10.1053/j.seminoncol.2005.12.010.

  PMID: 16473643 BACKGROUND

• Park SB, Kwok JB, Asher R, Lee CK, Beale P, Selle F, Friedlander M. Clinical and genetic predictors of paclitaxel neurotoxicity based on patient- versus clinician-reported incidence and severity of neurotoxicity in the ICON7 trial. Ann Oncol. 2017 Nov 1;28(11):2733-2740. doi: 10.1093/annonc/mdx491.

  PMID: 29117336 BACKGROUND

• Mols F, Beijers T, Vreugdenhil G, van de Poll-Franse L. Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review. Support Care Cancer. 2014 Aug;22(8):2261-9. doi: 10.1007/s00520-014-2255-7. Epub 2014 May 1.

  PMID: 24789421 BACKGROUND

• Molassiotis A, Cheng HL, Lopez V, Au JSK, Chan A, Bandla A, Leung KT, Li YC, Wong KH, Suen LKP, Chan CW, Yorke J, Farrell C, Sundar R. Are we mis-estimating chemotherapy-induced peripheral neuropathy? Analysis of assessment methodologies from a prospective, multinational, longitudinal cohort study of patients receiving neurotoxic chemotherapy. BMC Cancer. 2019 Feb 8;19(1):132. doi: 10.1186/s12885-019-5302-4.

  PMID: 30736741 BACKGROUND

• Carozzi VA, Canta A, Chiorazzi A. Chemotherapy-induced peripheral neuropathy: What do we know about mechanisms? Neurosci Lett. 2015 Jun 2;596:90-107. doi: 10.1016/j.neulet.2014.10.014. Epub 2014 Oct 22.

  PMID: 25459280 BACKGROUND

• Duggett NA, Griffiths LA, McKenna OE, de Santis V, Yongsanguanchai N, Mokori EB, Flatters SJ. Oxidative stress in the development, maintenance and resolution of paclitaxel-induced painful neuropathy. Neuroscience. 2016 Oct 1;333:13-26. doi: 10.1016/j.neuroscience.2016.06.050. Epub 2016 Jul 5.

  PMID: 27393249 BACKGROUND

• Erken HA, Koc ER, Yazici H, Yay A, Onder GO, Sarici SF. Selenium partially prevents cisplatin-induced neurotoxicity: a preliminary study. Neurotoxicology. 2014 May;42:71-5. doi: 10.1016/j.neuro.2014.04.002. Epub 2014 Apr 19.

  PMID: 24751598 BACKGROUND

• Argyriou AA, Chroni E, Koutras A, Ellul J, Papapetropoulos S, Katsoulas G, Iconomou G, Kalofonos HP. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology. 2005 Jan 11;64(1):26-31. doi: 10.1212/01.WNL.0000148609.35718.7D.

  PMID: 15642899 BACKGROUND

• Argyriou AA, Chroni E, Koutras A, Iconomou G, Papapetropoulos S, Polychronopoulos P, Kalofonos HP. Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation. J Pain Symptom Manage. 2006 Sep;32(3):237-44. doi: 10.1016/j.jpainsymman.2006.03.013.

  PMID: 16939848 BACKGROUND

• Ghoreishi Z, Esfahani A, Djazayeri A, Djalali M, Golestan B, Ayromlou H, Hashemzade S, Asghari Jafarabadi M, Montazeri V, Keshavarz SA, Darabi M. Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: a randomized double-blind placebo controlled trial. BMC Cancer. 2012 Aug 15;12:355. doi: 10.1186/1471-2407-12-355.

  PMID: 22894640 BACKGROUND

• Yim GW, Han KH, Lee ST, Lee M, Lee SM, Kim HS. Efficacy and safety of intravenous administration of high-dose selenium for preventing chemotherapy-induced peripheral neuropathy in platinum-sensitive recurrent ovarian cancer: a phase 3, double-blind, parallel group, randomized controlled pilot study. BMC Med. 2026 Feb 2. doi: 10.1186/s12916-026-04637-x. Online ahead of print.

  PMID: 41630017 DERIVED

• Park SJ, Yim GW, Paik H, Lee N, Lee S, Lee M, Kim HS. Efficacy and safety of intravenous administration of high-dose selenium for preventing chemotherapy-induced peripheral neuropathy in platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer: study protocol for a phase III, double-blind, randomized study. J Gynecol Oncol. 2021 Sep;32(5):e73. doi: 10.3802/jgo.2021.32.e73. Epub 2021 Jun 1.

  PMID: 34132071 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Peripheral Nervous System Diseases

Interventions

Sodium Selenite; Saline Solution; Sodium Chloride; Drug Therapy; Paclitaxel; Carboplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Selenious Acid; Selenium Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hee Seung Kim, MD/PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: December 8, 2019
• First Posted: December 17, 2019
• Study Start: December 24, 2019
• Primary Completion: April 30, 2023
• Study Completion: December 31, 2024
• Last Updated: June 26, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)