Itraconazole in Advanced Ovarian Cancer

Ovarian Carcinoma Clinical Trial

Official title:

The Possible Effect of Itraconazole as add-on Therapy to Paclitaxel and Carboplatin on the Treatment Outcome in Patients With Advanced Ovarian Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05591560
• Other study ID #: 35929/10/22
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 2022
• Est. completion date: October 2024

Study information

• Verified date: October 2022
• Source: Tanta University
• Contact: Ahmed ES Besheir, Master
• Phone: 00201060943386
• Email: ahmed.ezzat278[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, placebo controlled; parallel study that will be conducted on 66 female patients with advanced epithelial ovarian carcinoma (stage III and stage IV) to compare effect of adding Itraconazole to paclitaxel and carboplatin versus placebo to paclitaxel and carboplatin as regard overall response rate (ORR) and Disease control rate (DCR) and Quality of life (QOL) and the change in the serum concentrations of the biological markers.

Description:

This is a randomized, placebo controlled; parallel study that will be conducted on 66 female patients with advanced epithelial ovarian carcinoma (stage III and stage IV). The staging of the disease will be done according to 8th edition of American Joint Committee on Cancer (AJCC), TNM staging. The patients will be recruited from Oncology Department, Tanta University Hospital. The patients will receive a combination of paclitaxel and carboplatin chemotherapy with or without itraconazole. Randomization will be carried out based on hospital admission days where the patients will be randomized into the following two groups to compare effect of adding Itraconazole to paclitaxel and carboplatin versus placebo to paclitaxel and carboplatin.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 66
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Female patients Age >18 years old < 65 years old.

• Patients with histopathological and radiological based diagnosis of III, IV epithelial ovarian carcinoma according to 8th edition AJCC, primary tumor, regional nodes, metastasis (TNM) staging system.11

• Patients with Eastern Cooperative Oncology Group Performance Status of 0 or 1. 13

• Patients able to swallow and retain oral medications (without crushing, dissolving, or chewing tablets).

• Patients with adequate hematologic and organ function within 14 days before the first Cycle which can be defined by the following:

• Neutrophils (absolute neutrophil count (ANC) >1.5 X 10^9/L).

• Hemoglobin >9 g/dl.

• Platelet count >100,000/L.

• Serum albumin >3 g/dl.

• Total bilirubin 1.5 = of the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine transaminase ( ALT) = 2 of the upper limit of normal (ULN).

• Serum creatinine = 1.5 of the upper limit of normal (ULN) or estimated creatinine clearance >50 mL/min based on Cockcroft-Gault glomerular filtration rate estimation.

Exclusion Criteria:

• Presence of 2nd primary malignancy

• History of allergic reactions attributed to paclitaxel, carboplatin, and itraconazole or to compounds of similar chemical or biologic composition to itraconazole.

• Concurrent use of medications significantly affecting metabolism of itraconazole (certain anti-convulsants).

• Patients with hyperthyroidism (which would increase metabolism of itraconazole).

• Patients with grade = 2 neuropathy.

• Patients with Uncontrolled, concurrent medical illness.

• Patients with active hepatitis or symptomatic liver disease.

• History of or current evidence of uncontrolled cardiac ventricular dysfunction (congestive heart failure) or patients with class III and class IV heart failure according to New York Heart Association (NYHA).

• Pregnant or lactating female .

Related Conditions & MeSH terms

• Ovarian Carcinoma

Intervention

Drug:
• Itraconazole capsule
Oral itraconazole 400 mg (4 capsules, each of 100 mg) for 5 days (two days before chemotherapy, the day of chemotherapy after receiving it, and two days after chemotherapy) Day 1, 8, and 15 repeated every 21 days for 6 cycles for group II
• Placebo
4 placebo capsules for 5 days (two days before chemotherapy, the day of chemotherapy after receiving it, and two days after chemotherapy) Day 1, 8, and 15 repeated every 21 days for 6 cycles for group I

Locations

Country	Name	City	State
Egypt	Tanta University, Faculty of Pharmacy	Tanta

Sponsors (1)

Lead Sponsor	Collaborator
Tanta University

Country where clinical trial is conducted

Egypt, 

References & Publications (4)

Goenka L, Dubashi B, Selvarajan S, Ganesan P. Use of "Repurposed" Drugs in the Treatment of Epithelial Ovarian Cancer: A Systematic Review. Am J Clin Oncol. 2022 Apr 1;45(4):168-174. doi: 10.1097/COC.0000000000000900. — View Citation

Li CL, Fang ZX, Wu Z, Hou YY, Wu HT, Liu J. Repurposed itraconazole for use in the treatment of malignancies as a promising therapeutic strategy. Biomed Pharmacother. 2022 Oct;154:113616. doi: 10.1016/j.biopha.2022.113616. Epub 2022 Aug 30. Review. — View Citation

Mohamed AW, Elbassiouny M, Elkhodary DA, Shawki MA, Saad AS. The effect of itraconazole on the clinical outcomes of patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy: a randomized controlled study. Med Oncol. 2021 Feb 9;38(3):23. doi: 10.1007/s12032-021-01475-0. — View Citation

Nunes M, Henriques Abreu M, Bartosch C, Ricardo S. Recycling the Purpose of Old Drugs to Treat Ovarian Cancer. Int J Mol Sci. 2020 Oct 20;21(20). pii: E7768. doi: 10.3390/ijms21207768. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change between 2 groups in overall response rate and disease control rate	The change between 2 groups in overall response rate and disease control rate using the Response Evaluation Criteria in Solid Tumors (RECIST), version. 1.1.	1 week after the end of chemotherapy cycle 3 and 6 (each cycle is 21 days) and every 2 to 4 months after the end of 6 chemotherapy cycles (each cycle is 21 days) for 1 year
Secondary	The change in the serum concentrations of the biological markers (CA-125, VEGFR-2, P-glycoprotein).	Serum cancer antigen-125 (CA-125) level which will be assessed at baseline for all patients, after the third chemotherapy cycle and after the sixth chemotherapy cycle if it is positive at initial presentation.; Serum vascular endothelial growth factor receptor-2 (VEGFR-2) level by ELISA which will be assessed at baseline and after the sixth chemotherapy cycle.; Serum P-glycoprotein level by ELISA which will be assessed at baseline and after the sixth chemotherapy cycle.	1 week after the end of chemotherapy cycle 3 and 6 (each cycle is 21 days) and every 2 to 4 months after the end of 6 chemotherapy cycles (each cycle is 21 days) for 1 year