Vitamin D Status and Clinical Outcomes in Locally Advanced Cervical Cancer

NCT07743918 | Recruiting

• 1 other identifier: CERVITAL-2025
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Background. Definitive chemoradiotherapy represents the standard therapeutic approach for the management of locally advanced cervical cancer. Vitamin D plays an important role in the regulation of cellular growth and differentiation, immune system function, and the modulation of inflammatory processes. Hypovitaminosis D may be associated with the development of cervical cancer, whereas its impact on the effects of oncological treatment remains insufficiently elucidated. The aim of this study is to investigate the predictive significance of vitamin D in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy. Methods. This study is designed as a clinical, observational, prospective cohort study. Patients with locally advanced cervical cancer undergoing definitive chemoradiotherapy at the Clinic for Radiation Oncology, University Clinical Center Kragujevac, will be enrolled. Vitamin D concentrations will be measured before the initiation of treatment in both serum and cervical lavage samples. Baseline vitamin D levels will be analyzed in relation to treatment outcome and the occurrence of acute radiation toxicity. In addition, vitamin D concentrations will be evaluated in the context of clinical and morphological parameters, therapeutic response, and treatment-related toxicity. Expected Results. This study will enable an assessment of the actual significance of pretreatment vitamin D concentrations in serum and cervical lavage as a potential novel biomarker in relation to chemoradiosensitivity and/or chemoradioresistance of cervical cancer, as well as the response of organs at risk, in patients with locally advanced disease.

Conditions

Vitamin D Concentration; Locally Advanced Cervical Cancer

Keywords

Locally advanced cervical cancer;; vitamin D;; hypovitaminosis D;; serum vitamin D;; cervical lavage;; chemoradiotherapy;; radiotherapy;; cisplatin;; brachytherapy;; treatment response;; radiation toxicity;; RECIST 1.1;; CTCAE;; chemoradiosensitivity;; chemoradioresistency

Outcome Measures

Primary Outcomes (1)

• Complete therapeutic response after definitive chemoradiotherapy

  The proportion of patients achieving complete therapeutic response after definitive concurrent chemoradiotherapy. Treatment response will be assessed by pelvic magnetic resonance imaging and clinical examination, according to RECIST 1.1 criteria.

  Five months after the last radiotherapy fraction.

Secondary Outcomes (7)

• Clinically significant acute radiation toxicity

  First radiotherapy fraction until 90th day (acute toxicity).

• Severity of acute radiation toxicity

  First radiotherapy fraction until 90th day.

• Association between pretreatment serum vitamin D concentration and treatment response

  Baseline before treatment initiation and five months after the last radiotherapy fraction.

• Association between pretreatment cervical lavage vitamin D concentration and treatment response

  Baseline before treatment initiation and five months after the last radiotherapy fraction.

• Association between pretreatment vitamin D concentration and acute radiation toxicity

  Baseline before treatment initiation and 90th day.

Study Arms (1)

Locally Advanced Cervical Cancer Cohort

Patients with histopathologically confirmed locally advanced cervical cancer, FIGO 2018 stage IIB-IVA, treated with definitive concurrent chemoradiotherapy. Pretreatment vitamin D concentrations will be measured in serum and cervical lavage fluid before treatment initiation, and patients will be followed for treatment response and acute radiation toxicity.

Diagnostic Test: Pretreatment Vitamin D Assessment in Serum and Cervical Lavage Fluid

Interventions

Pretreatment Vitamin D Assessment in Serum and Cervical Lavage Fluid DIAGNOSTIC_TEST

Vitamin D concentrations will be measured before the initiation of definitive chemoradiotherapy in serum and cervical lavage fluid using chemiluminescence, as the standard institutional laboratory method. Baseline vitamin D levels will be analyzed in relation to treatment response, acute radiation toxicity, and selected clinical, morphological, treatment-related, and socio-demographic parameters.

Locally Advanced Cervical Cancer Cohort

Eligibility Criteria

• Age: 18 Years - 80 Years
• Gender Eligibility Details: Participants eligible for this study are individuals who self-identify as female and have histopathologically confirmed locally advanced cervical cancer.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will include adult individuals who self-identify as female, aged 18 to 80 years, with histopathologically confirmed locally advanced cervical cancer, FIGO 2018 stage IIB-IVA, who are planned for definitive concurrent chemoradiotherapy at the Clinic for Radiation Oncology, University Clinical Center Kragujevac. All participants must provide written informed consent and be eligible for standard treatment consisting of external beam radiotherapy, high-dose-rate brachytherapy, and weekly cisplatin-based chemotherapy.

You may qualify if:

• Female patients aged 18 to 80 years.
• Histopathologically confirmed cervical cancer.
• Locally advanced disease, FIGO 2018 stage IIB to IVA.
• Eastern Cooperative Oncology Group performance status 0-1.
• Planned treatment with definitive concurrent chemoradiotherapy.
• Signed informed consent.
• Ability to comply with study procedures and follow-up visits.

You may not qualify if:

• Age under 18 years.
• Pregnancy or lactation.
• Previous or synchronous diagnosis of another pelvic or abdominal malignancy.
• Previous chemotherapy.
• Previous radiotherapy.
• Previous treatment with immune checkpoint inhibitors.
• Current or recent vitamin D supplementation.
• Interrupted oncological treatment.
• Failure to attend scheduled follow-up visits.
• Incomplete medical documentation.

Sponsors & Collaborators

• University of Kragujevac: lead

Study Sites (1)

University Clinical Center Kragujevac

Kragujevac, Šumadija, 34000, Serbia

RECRUITING

Related Links

• Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74(3):229-263.
• National Comprehensive Cancer Network. Cervical Cancer. Version 2.2026.
• Mehta AM, Mooij M, Branković I, Ouburg S, Morré SA, Jordanova ES. Cervical carcinogenesis and immune response gene polymorphisms: a review. J Immunol Res 2017;2017:8913860.
• 5\) Li R, Liu Y, Yin R, et al. The dynamic alternation of local and systemic tumor immune microenvironment during concurrent chemoradiotherapy of cervical cancer: a prospective clinical trial. Int J Radiat Oncol Biol Phys 2021;110(5):1432-1441.
• Dong H, Chen S, Liang X, et al. Vitamin D and its receptors in cervical cancer. J Cancer 2024;15(4):926-938.
• Zhang Z, Yu X, Cheng G. Vitamin D sensitizes cervical cancer to radiation-induced apoptosis by inhibiting autophagy through degradation of Ambra1. Cell Death Discov 2025;11(1):1.
• Wu Q, Zhang L, Sun Y, Ying J. Vitamin D-regulated miR-589-3p in patients with cervical cancer predicts patient prognosis and is involved in tumor progression. Nutr Cancer 2024;76(9):840-848.
• Suardi D, Judistiani RTD, Rinaldi M, et al. Impact of cholecalciferol supplementation on radiotherapy outcomes in advanced cervical cancer. Med Sci Monit 2025;31:e945964.
• National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). Version 6.0.
• Schwartz LH, Litière S, de Vries E, et al. RECIST 1.1: update and clarification from the RECIST committee. Eur J Cancer 2016;62:132-137.
• Fields EC, Bosch WR, Albuquerque KV, et al. Consensus guidelines for delineation of clinical target volumes for intensity modulated radiation therapy for intact cervical cancer: an update. Pract Radiat Oncol 2025;15(2):171-179.
• Cibula D, Raspollini MR, Planchamp F, et al. ESGO/ESTRO/ESP guidelines for the management of patients with cervical cancer - update 2023. Int J Gynecol Cancer 2023;33(5):649-666.
• Grover S, Lichter KE, Likhacheva A, et al. The American Brachytherapy Society and Indian Brachytherapy Society consensus statement for the establishment of high-dose-rate brachytherapy programs for gynecological malignancies in low- and middle-income

MeSH Terms

Conditions

Vitamin D Deficiency; Radiation Injuries

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Wounds and Injuries

Study Officials

• Marija Živković Radojević, MD, PhD, Radiation Oncologist

  Faculty of Medical Sciences, University of Kragujevac, Serbia, University Clinical Centre Kragujevac, Center for radiation oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marija Živković Radojević, MD, PhD, Radiation Oncologist

CONTACT

+381658384450; makizivkovicmarija@gmail.com

Neda Milosavljević, MD, PhD, Radiation Oncologist

CONTACT

+381638429691; neda.milosavljevic@yahoo.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 7 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 13, 2026
• First Posted: August 4, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 10, 2028
• Study Completion (Estimated): September 1, 2034
• Last Updated: August 4, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)