Itraconazole in Advanced Ovarian Cancer

Not Applicable

Not yet recruiting

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.

Recruitment & 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 .

Arm && Interventions

Group	Intervention	Description
Group II Itraconazole group	Itraconazole capsule	Group II: (Itraconazole group; n=33) which will be treated with chemotherapy which includes paclitaxel 60 mg/m2 IV over 1 hour followed by carboplatin AUC 2 IV over 30 minutes Day 1, 8, and 15 repeated every 21 days for 6 cycles 12 plus 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).
Group I Placebo group	Placebo	Group I (Placebo group; n=33) which will be treated with chemotherapy which includes paclitaxel 60 mg/m2 IV over 1 hour followed by carboplatin area under the curve 2 (AUC 2) IV over 30 minutes Day 1, 8, and 15 which will be repeated every 21 days for 6 cycles 12 plus 4 placebo capsules for 5 days (two days before chemotherapy, the day of chemotherapy after receiving it, and two days after chemotherapy).

Primary Outcome Measures

Name	Time	Method
The change between 2 groups in overall response rate and disease control rate	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	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.

Secondary Outcome Measures

Name	Time	Method
The change in the serum concentrations of the biological markers (CA-125, VEGFR-2, P-glycoprotein).	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	* 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.