High Dose Inorganic Selenium for Preventing Chemotherapy Induced Peripheral Neuropathy

Ovarian Cancer Clinical Trial

— SELENIUM  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04201561
• Other study ID #: SELENIUM trial
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 24, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2023
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 68
• Est. completion date: December 31, 2024
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Chemotherapy-induced Peripheral Neuropathy
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Peripheral Nervous System Diseases
• Primary Peritoneal Carcinoma
• Recurrence
• Recurrent Ovarian Carcinoma

Intervention

Drug:
• sodium selenite pentahydrate
High-dose inorganic selenium (2000 µg/40 ml) will be administered before chemotherapy in patients assigned to the experimental group.
• Normal saline
Normal saline (40 ml) will be administered before chemotherapy in patients assigned to the control group.
• Chemotherapy
Paclitaxel (175mg/m2), carboplatin (AUC 5.0 or 6.0) IV, and bevacizumab IV (15mg/kg) D1, every three weeks.

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Boryung Pharmaceutical Co., Ltd

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. Erratum In: Neurosci Lett. 2015 Jun 2;596():108. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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
Secondary	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