Itraconazole in Advanced Ovarian Cancer

Sponsor

Tanta University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05591560

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Carcinoma	Drug: Itraconazole capsule Drug: Placebo	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

66 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Group I Placebo group 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 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
Active Comparator: Group II Itraconazole group 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 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

Arm

Intervention/Treatment

Placebo Comparator: Group I Placebo group

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

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

Active Comparator: Group II Itraconazole group

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

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

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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 .