Biological Effect of Vitamin D in Patients With Urothelial Carcinoma

NCT04197089 | Completed Phase 4 DMC

• 1 other identifier: VitDURO-AECC17-01
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The study population will be 50 women or men diagnosed with urothelial cancer candidates to undergo cystectomy as part of their antitumor treatment. The main objective of the study is to determine the biological effect of Vitamin D on tumor tissue phenotype; for thus, all subjects enrolled in the study will take Vitamin D supplementation 4 weeks prior undergoing surgery. Urothelial tissue will be obtained from the surgical procedure and will be studied for the Vitamin D effect on cancer cell, compared with that urothelial tissue biopsy obtained in the moment of cancer diagnosis.

Conditions

Urothelial Carcinoma

Keywords

Cancer; Urinary tract; Cystectomy; Vitamin D; Tissue phenotype

Outcome Measures

Primary Outcomes (2)

• Analysis of gene expression in urothelial tumor tissue, comparing initial tumor biopsy and cystectomy tumor tissue exposed to Vitamin D (reported in number of mRNA copies)

  Measurement of mRNA levels of differentiation and Vitamin D response markers (FGFR3, CDH1, CDKN1A/p21, THBD, VDR, G0S2 and GAPDH), determined by quantitative reverse transcription PCR (RT-qPCR)

  One year post-cystectomy

• Analysis of protein expression in urothelial tumor tissue, comparing initial tumor biopsy and cystectomy tumor tissue exposed to Vitamin D (reported in arbitrary units)

  Measurement of expression and distribution of differentiation and Vitamin D response markers (FGFR3, CDH1, CDH2, VDR, Ki67, CDKN1A/p21, KRT5, KRT14, KRT20 and UPK), determined by immunohistochemistry (IHC)

  One year post-cystectomy

Secondary Outcomes (2)

• Analysis of gene expression in peripheral blood leukocytes (reported in number of mRNA copies)

  One to five months post-cystectomy

• Levels of serum 25(OH)Vitamin D (reported in ng/ml)

  Ten weeks

Study Arms (1)

Vitamin D treatment

EXPERIMENTAL

Treatment with 10.000 IU or 50.000 IU Vitamin D weekly during 4 weeks

Drug: Vitamin D

Interventions

Vitamin D DRUG

First dose of 10.000 IU Vitamin D at baseline visit for all patients; stratification of treatment (10.000 or 50.000 IU Vitamin D) depending base 25(OH)Vitamin D levels. Treatment weekly during 4 weeks before scheduled cystectomy

Also known as: Cholecalciferol, Colecalciferol

Vitamin D treatment

Eligibility Criteria

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

You may qualify if:

• Men and women older than 18 years
• Patients willing and able to read and understand the patient's information sheet and give their consent
• Histologically confirmed diagnosis of urothelial non-muscle-invasive bladder cancer (T1 high grade and/or carcinoma in situ), and patients with muscle-invasive or high urinary tract carcinoma without evidence of distant metastasis (T2-4N0M0)
• Candidate patients to undergo treatment by radical cystectomy or nephroureterectomy as part of conventional tumor treatment.
• Not having received any antitumor treatment during the 4 weeks prior the administration of Vitamin D
• Life expectancy longer than 6 months
• Karnofsky Index \> 70%
• Confirmed adequate bone marrow, kidney and liver functions by:
• Leukocyte count \> 4.000
• Platelet count \> 100.000
• Haemoglobin levels \> 10 gr/dl
• Serum bilirubin levels \< 1,5X the upper limit of normality
• AST and ALT levels \< 2,5X the upper limit of normality
• Alkaline Phosphatase levels \< 5X the upper limit of normality
• Serum creatinine levels ≤ 2 mg/dl, and/or GFR ≥ ml/min/1.73m2 estimated by MDRD-4 IDMS or CKD-EPI evaluation

You may not qualify if:

• Ade older than 80 years
• Patients with non-urothelial histology. Those with mixed histology may be included if the urothelial component is the predominant (\> 50%)
• Administration of neoadjuvant chemotherapy
• Administration of radiotherapy during the period between TUR and surgery
• Medical history of another neoplasm diagnosed in the previous 3 years (except carcinoma in situ or non-melanoma cutaneous carcinoma). It may be included those patients with history of other neoplasms, provided that after receiving radical treatment do not relapsed
• History of hypersensitivity to Vitamin D
• History of hypercalcemia and/or hypercalciuria
• Situation of hypervitaminosis (25-OH Vitamin D \> 50 ng/ml)
• Previous treatment with Vitamin D in the last 6 months
• Chronic treatment with corticosteroids
• Other serious diseases or medical processes such as: infection that requires systemic anti-infective treatment or not controlled serious medical processes, including severe heart disease (episodes of ischemic heart disease in the last 6 months, cardiac arrhythmia or heart failure)
• Medical history of sarcoidosis or parathyroid disease
• History of malabsorption syndrome (for example pancreatic insufficiency, celiac disease or Crohn's disease), history of small bowled resection or any medical condition that may interfere with Vitamin D absorption
• Patients who are expected to administer nutritional supplements containing Vitamin D, or who are being treated with drugs (or combination of drugs) that contain Vitamin D
• Pregnancy

Sponsors & Collaborators

• Germans Trias i Pujol Hospital: lead
• Spanish Clinical Research Network - SCReN: collaborator
• Centro Nacional de Investigaciones Oncologicas CARLOS III: collaborator
• Fundació Institut Germans Trias i Pujol: collaborator

Study Sites (1)

Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Neoplasms

Interventions

Vitamin D; Cholecalciferol

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholestenes; Cholestanes; Sterols; Membrane Lipids; Lipids

Study Officials

• Francisco Xavier Real, MD, PhD

  Centro Nacional de Investigaciones Oncologicas CARLOS III (CNIO)

  STUDY CHAIR

• Albert Font Pous, MD, PhD

  Institut Català Oncologia (ICO)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Treatment stratified with 10.000 IU or 50.000 IU Vitamin D depending of baseline 25(OH)Vitamin D plasmatic levels

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 12, 2019
• Study Start: February 11, 2020
• Primary Completion: November 22, 2021
• Study Completion: November 22, 2021
• Last Updated: August 3, 2022

Record last verified: 2022-08

Locations

ES (1)