Clinical trial NCT05451576: Sodium Selenite Supplementation in Patients With Head and Neck Cancer
Official title: The Role of Sodium Selenite Supplementation in Patients With Locally Advanced Head and Neck Cancer Undergoing Concurrent Chemoradiotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Head and Neck Squamous Cell Carcinoma
Selenium
Sodium Selenite
Keywords: Sodium selenite
Selenium
chemoradiotherapy
head and neck cancer
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2022-07-11
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Toxicities
timeFrame: Week 1 to Week 8
measure: Pain assessment
timeFrame: Week 1 to Week 8
measure: Quality of life changes
timeFrame: Week 1 to Week 8
measure: Serum concentration changes of selenium
timeFrame: Week 1 to Week 8
measure: Changes of albumin
timeFrame: Week 1 to Week 12
measure: Changes of transferrin
timeFrame: Week 1 to Week 12
measure: Changes of total cholesterol
timeFrame: Week 1 to Week 12
measure: Change of interferon-γ (IFNγ)
timeFrame: Week 1 to Week 8
measure: Changes of tumor necrosis factor-α (TNFα)
timeFrame: Week 1 to Week 8
measure: Changes of interleukin-2 (IL-2)
timeFrame: Week 1 to Week 8
measure: Changes of interleukin-6 (IL-6)
timeFrame: Week 1 to Week 8
measure: Changes of granzyme B
timeFrame: Week 1 to Week 8
measure: Immune cells changes during concurrent chemoradiotherapy
timeFrame: Week 1 to Week 8
Secondary outcomes:
measure: Disease-free survival
timeFrame: 0 to 3 years
measure: Overall survival
timeFrame: 0 to 3 years
Other outcomes:
Locations:
city: Keelung
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Chang Gung Memorial Hospital
name: Hang Huong Ling, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
citation: 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.
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.
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.
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.