Study to assess the effects of vitamin D on tumor tissue in urinary bladder cancer

Phase 1

• Conditions: Patients with resectable urinary tract urothelial carcinoma candidates to radical cystectomy o nephroureterectomy.; MedDRA version: 20.0Level: LLTClassification code 10046718Term: Urothelial carcinoma bladder stage I, with cancer in situSystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10046720Term: Urothelial carcinoma bladder stage IISystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10046721Term: Urothelial carcinoma bladder stage IIISystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10046724Term: Urothelial carcinoma ureter localSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000695-28-ES
• Lead Sponsor: Hospital Universitari Germans Trias i Pujol

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-05-21
• Last Update Posted: 26 September 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Men and women older than 18 years.
2. Patients are willing and able to read and understand the patient’s information sheet and give their consent for participation in the study, before initiating any protocol specific procedure.
3. 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).
4. Candidate patients to undergo treatment by radical cystectomy or nephroueterectomy as part of conventional tumor treatment.
5. Not having received any antitumor treatment during the 4 weeks prior the administration of Vitamin D3.
6. Life expectancy longer than 6 months.
7. Karnofsky Index > 70%.
8. 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 Glomerular Filtration Rate =45 mL/min/1,73m2 estimated by MDRD-4 IDMS or CKD-EPI evaluation.
9. Plasma calcium levels between 8,8 and 10,6 mg/dL, and 24 hours urine calcium levels between 100 and 300 mg/24h.
10. Women of childbearing potential should use a highly effective contraceptive method according the Clinical Trial Facilitation Group (such as combined hormonal contraceptives or IUD), and should continue its use for 90 days after the last dose of Vitamin D3.
11. Males in fertile age, with a potentially fertile partner, should use a contraceptive method such as sexual abstinence or barrier method (condom), throughout the clinical trial and up to 90 days after the end of treatment, or be vasectomized.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1. Age older than 80 years.
2. Patients with non-urothelial histology. Those with mixed histology (urothelial histology combined with another histological type) may be included if the urothelial component is the predominant (>50%).
3. Administration of neoadjuvant chemotherapy.
4. Administration of radiotherapy during the period between TUR and surgery.
5. 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.
6. History of hypersensitivity to Vitamin D.
7. History of renal lithiasis larger than 5 mm or symptomatic in the year prior its inclusion in the study, and/or nephrocalcinosis.
8. History of hypercalcemia and/or hypercalciuria.
9. Situation of hypervitaminosis (25-OH Vitamin D > 50 ng/mL).
10. Previous treatment with Vitamin D3 in the last 6 months.
11. Chronic treatment with corticosteroids.
12. Other serious diseases or medical processes such as:
- Infection that requires systemic anti-infective treatment.
- Not controlled serious medical process, including severe heart disease (episodes of ischemic heart disease in the last 6 months, cardiac arrhythmia or heart failure).
13. Medical history of sarcoidosis or parathyroid disease.
14. History of malabsorption syndrome (for example pancreatic insufficiency, celiac disease or Crohn’s disease), history of small bowel resection or any medical condition that may interfere with Vitamin D absorption.
15. 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.
16. Pregnancy.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the biological effect of weekly treatment with Vitamin D3 (10.000 UI or 50.000 UI according baseline levels) on tumor phenotype (sample comparison between transurethral resection and cystectomy or nephroureterectomy).;Secondary Objective: 1. To determine the biological effect of Vitamin D3 treatment on peripheral blood leukocyte gene expression as a marker of treatment sensitivity.<br>2. To compare the biological effects of Vitamin D3 on tumor phenotype and peripheral blood leukocyte gene expression, regarding plasma levels prior and after Vitamin D3 administration.;Primary end point(s): Tumor expression of differentiation and Vitamin D response markers (RNA and protein), comparing pre- versus post- intervention with Vitamin D.;Timepoint(s) of evaluation of this end point: Post-surgical intervention.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Expression of Vitamin D target genes in peripheral blood leukocytes (RNA), comparing pre- versus post-intervention with Vitamin D.<br>- Vitamin D plasma levels, comparing pre- versus post- study inclusion.;Timepoint(s) of evaluation of this end point: At the end of the study.