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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05451576
Other study ID # 202000865A3
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date August 12, 2020
Est. completion date June 30, 2024

Study information

Verified date August 2023
Source Chang Gung Memorial Hospital
Contact Li-Ting Lian
Phone +886-224329292
Email liting@cgmh.org.tw
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The micronutrient selenium is an essential trace element in the human body. There are more than 25 proteins in the human body contain selenium, such as glutathione peroxidase and selenoprotein, which regulate the body's antioxidant and anti-inflammatory properties. Previous literatures had shown cancer patients have lower serum selenium concentrations than normal people, and lower serum selenium levels may be associated with increased cancer mortality. More than 50% of patients with locally advanced head and neck cancer are malnourished before treatment, and these patients often have deficiency of trace elements, including selenium. In these malnourished patients, they may have to endure increased treatment toxicity and treatment interruption when receiving standard concurrent chemoradiotherapy (CCRT). Interruption of treatment may lead to reduced therapeutic efficacy and compromised survival and recurrence rate. Several small studies have investigated whether oral administration of sodium selenite in patients with head and neck cancer undergoing radiation therapy can improve side effects and affect survival rates, but the results are inconsistent. Our study will use the intravenous form of sodium selenite (Zelnite®) to investigate the effect of selenium on the treatment outcomes of locally advanced head and neck cancer patients undergoing CCRT, such as therapy-related toxicities, quality of life, changes in selenium concentration in blood, nutritional, inflammation and immune markers, and tracking long-term survival and recurrence rates.


Description:

Selenium is an essential trace element for humans. It is involved in redox regulation, antioxidant functions, membrane integrity, and protection against DNA injury. In both animal models and human studies, it has been shown that selenium has cancer-protective effects and cytoprotective activities. Some mechanisms have been proposed to explain the anti-cancer effects of selenium, which include the antioxidant properties by selenoproteins, induction of conjugating enzymes that detoxify carcinogens, enhancement of the immune response, alterations in DNA methylation and blockage of the cell cycle to allow DNA repair. There has been conflicting response regarding selenium supplementation on the reduction of toxicity, antitumor efficacy and their quality of life in patients receiving radiotherapy. In the studies by Kiremidjian-Schumacher et al. and Elango et. al, sodium selenite supplementation was shown to significantly enhance cell-mediated immune responsiveness and improve defense systems in head and neck cancer patients. Micke et al. and Zimmerman et al. demonstrated the quality of life of patients suffering from head and neck cancer with lymphedema significantly improved after selenium supplementation. In the study by Büntzel et al., selenium supplementation reduced the radiation-associated side-effects of dysphagia developments in patients with head and neck cancer patients. However, some studies showed negative response of selenium supplementation in head and neck cancer patients. Weijl et al. showed oral selenium supplementation did not show improvement in cisplatin-induced toxicity or response rate in cancer patients. In the study by Mix et al., addition of oral selenium supplementation was well-tolerated but did not lower the incidence of severe mucositis or improve quality of life or survival outcomes in head and neck cancer patients undergoing concurrent chemoradiation (CRT). An early systematic review in Cochrane demonstrated there was still insufficient evidence to conclude efficacy of selenium in alleviating the side effects of chemotherapy or radiotherapy treatments. The aim of this study is to investigate the effect of intravenous selenium supplementation on the treatment outcome of head and neck patients undergoing CCRT (toxicities, quality of life, overall survival, progression-free survival), selenium concentration changes during CCRT, and its correlation with nutritional, inflammation and immune markers.


Recruitment information / eligibility

Status Recruiting
Enrollment 60
Est. completion date June 30, 2024
Est. primary completion date December 31, 2023
Accepts healthy volunteers No
Gender All
Age group 20 Years to 75 Years
Eligibility Inclusion Criteria: - Histological proven head and neck squamous cell carcinoma (oral cavity, oropharynx, hypopharynx, larynx, or metastatic cervical lymphadenopathy of unknown primary origin) who were scheduled for adjuvant or primary concurrent chemoradiotherapy (CCRT). - American Joint Committee on Cancer 8th edition stage III, IVA, and IVB patients. - Age 20-75 years old. - Adequate hematopoietic or organ function (leukocyte count = 3.0 x 109/L, hemoglobin = 10 g/dL, platelet count = 100 x109/L, serum bilirubin level = 1.5 mg/dL, alanine aminotransferase (ALT) and aspartate aminotransferase levels (AST) = 3 x upper limit of normal, and serum creatinine level = 1.6 mg/dL or creatinine clearance = 60 mL/min/1.73m2). - ECOG performance status grade?2. - Subjects understand this study, agree to join this study and are able to sign the written inform consent form. Exclusion Criteria: - Nasopharyngeal cancer. - History of selenium allergy or intolerance. - Received selenium supplementation in recent 1 month. - Uncontrolled infection - according to PI diagnosis - Heart failure - New York Heart Association class IV - Impaired liver function (serum total bilirubin > 2 x upper limit of normal (ULN), ALT and/or AST > 5 x ULN). - Impaired renal function: serum creatinine > 1.5 x ULN. - Inadequate bone marrow function (white blood cell count < 2,500 / mm3 (<2.5 x 10^9/L), platelets < 100,000 / mm3 (< 100 x 10^9/L) and hemoglobin < 10 g/dL).

Study Design


Related Conditions & MeSH terms


Intervention

Dietary Supplement:
Zelnite®
2pc intravenous Zelnite® will be given for 7 weeks (5 days/week).
Placebo
Placebo will be given for 7 weeks (5 days/week).

Locations

Country Name City State
Taiwan Chang Gung Memorial Hospital Keelung

Sponsors (1)

Lead Sponsor Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (8)

Buntzel J, Riesenbeck D, Glatzel M, Berndt-Skorka R, Riedel T, Mucke R, Kisters K, Schonekaes KG, Schafer U, Bruns F, Micke O. Limited effects of selenium substitution in the prevention of radiation-associated toxicities. results of a randomized study in head and neck cancer patients. Anticancer Res. 2010 May;30(5):1829-32. — View Citation

Dennert G, Horneber M. Selenium for alleviating the side effects of chemotherapy, radiotherapy and surgery in cancer patients. Cochrane Database Syst Rev. 2006 Jul 19;2006(3):CD005037. doi: 10.1002/14651858.CD005037.pub2. — View Citation

Elango N, Samuel S, Chinnakkannu P. Enzymatic and non-enzymatic antioxidant status in stage (III) human oral squamous cell carcinoma and treated with radical radio therapy: influence of selenium supplementation. Clin Chim Acta. 2006 Nov;373(1-2):92-8. doi: 10.1016/j.cca.2006.05.021. Epub 2006 May 19. — View Citation

Kiremidjian-Schumacher L, Roy M, Glickman R, Schneider K, Rothstein S, Cooper J, Hochster H, Kim M, Newman R. Selenium and immunocompetence in patients with head and neck cancer. Biol Trace Elem Res. 2000 Feb;73(2):97-111. doi: 10.1385/BTER:73:2:97. — View Citation

Micke O, Bruns F, Mucke R, Schafer U, Glatzel M, DeVries AF, Schonekaes K, Kisters K, Buntzel J. Selenium in the treatment of radiation-associated secondary lymphedema. Int J Radiat Oncol Biol Phys. 2003 May 1;56(1):40-9. doi: 10.1016/s0360-3016(02)04390-0. — View Citation

Mix M, Singh AK, Tills M, Dibaj S, Groman A, Jaggernauth W, Rustum Y, Jameson MB. Randomized phase II trial of selenomethionine as a modulator of efficacy and toxicity of chemoradiation in squamous cell carcinoma of the head and neck. World J Clin Oncol. 2015 Oct 10;6(5):166-73. doi: 10.5306/wjco.v6.i5.166. — View Citation

Weijl NI, Elsendoorn TJ, Lentjes EG, Hopman GD, Wipkink-Bakker A, Zwinderman AH, Cleton FJ, Osanto S. Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatin-based chemotherapy: a randomised, double-blind, placebo-controlled study. Eur J Cancer. 2004 Jul;40(11):1713-23. doi: 10.1016/j.ejca.2004.02.029. — View Citation

Zimmermann T, Leonhardt H, Kersting S, Albrecht S, Range U, Eckelt U. Reduction of postoperative lymphedema after oral tumor surgery with sodium selenite. Biol Trace Elem Res. 2005 Sep;106(3):193-203. doi: 10.1385/BTER:106:3:193. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Toxicities Mucositis, pharyngitis, dermatitis, xerostomia, fatigue, infection, and cytopenia by Common Terminology Criteria for Adverse Events version 5 (CTCAE v5.0) Week 1 to Week 8
Primary Pain assessment Visual analogue scale (VAS): score ranges 0-10 (higher value indicates worse outcome) Week 1 to Week 8
Primary Quality of life changes European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-HN43), reported in mean values (higher value indicates worse outcome) Week 1 to Week 8
Primary Serum concentration changes of selenium Serum levels of selenium during concurrent chemoradiotherapy Week 1 to Week 8
Primary Changes of albumin Serum albumin (g/dL) changes during concurrent chemoradiotherapy Week 1 to Week 12
Primary Changes of transferrin Serum transferrin (mg/dL) changes during concurrent chemoradiotherapy Week 1 to Week 12
Primary Changes of total cholesterol Total cholesterol (mg/dL) changes during concurrent chemoradiotherapy Week 1 to Week 12
Primary Change of interferon-? (IFN?) IFN? (pg/mL) changes during concurrent chemoradiotherapy Week 1 to Week 8
Primary Changes of tumor necrosis factor-a (TNFa) TNFa (pg/mL) changes during concurrent chemoradiotherapy Week 1 to Week 8
Primary Changes of interleukin-2 (IL-2) IL-2 (pg/mL) changes during concurrent chemoradiotherapy Week 1 to Week 8
Primary Changes of interleukin-6 (IL-6) IL-6 (pg/mL) changes during concurrent chemoradiotherapy Week 1 to Week 8
Primary Changes of granzyme B Granzyme B (pg/mL) changes during concurrent chemoradiotherapy Week 1 to Week 8
Primary Immune cells changes during concurrent chemoradiotherapy By using Maxpar Direct Immune Profiling Assay to identify 30 subsets of immune cells Week 1 to Week 8
Secondary Disease-free survival 0 to 3 years
Secondary Overall survival 0 to 3 years
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