Clinical trial NCT05591560: Itraconazole in Advanced Ovarian Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Ovarian Carcinoma
Keywords: Itraconazole
Paclitaxel
Carboplatin
Chemotherapy
Epithelial
Ovarian
Carcinoma
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2022-10-24
Enrollment: 66
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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 .

Primary outcomes:
measure: The change between 2 groups in overall response rate and disease control rate
timeFrame: 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 outcomes:
measure: The change in the serum concentrations of the biological markers (CA-125, VEGFR-2, P-glycoprotein).
timeFrame: 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
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Tanta University, Faculty of Pharmacy
Study officials:
affiliation: Tanta University
name: Tarek M Mostafa, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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):7768. doi: 10.3390/ijms21207768.
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.
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.