Itraconazole in Advanced Ovarian Cancer

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Ovarian Carcinoma

Intervention / Treatment
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* Drug: Itraconazole capsule
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group I Placebo group<br>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). | Drug: Placebo<br>* 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<br>|
| Active Comparator: Group II Itraconazole group<br>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). | Drug: Itraconazole capsule<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Itraconazole, Paclitaxel, Carboplatin, Chemotherapy, Epithelial, Ovarian, Carcinoma