A Phase I/II Study of Paclitaxel Plus Carboplatin Plus Vorinostat in Recurrent Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title: A Phase I/II Non-Comparative Study of Paclitaxel Plus Carboplatin in Combination With Vorinostat in Patient With Advanced, Recurrent, Epithelial Ovarian Cancer

Status Recruiting

Clinical Trial Summary

TITLE:A Phase II non-comparative study of paclitaxel plus carboplatin in combination with Vorinostat in patients with advanced, recurrent epithelial ovarian cancer. INDICATION:Second-line treatment of patients with recurrent platinum-sensitive epithelial ovarian cancer. RATIONALE:Recurrent epithelial ovarian cancer is today an incurable disease. The current standard of care consists of systemic chemotherapy using either carboplatin plus paclitaxel (in platinum-sensitive patients) or single agent chemotherapy with agents like liposomal doxorubicin, topotecan, weekly paclitaxel or gemcitabine (platinum non-sensitive patients). The outcome for patients with advanced ovarian cancer nevertheless remains poor.Preclinical evidence suggests that vorinostat, a potent histone deacetylase (HDAC) inhibitor, may potentiate the antitumor activity of paclitaxel and/or carboplatin. The study will assess whether the addition of vorinostat to paclitaxel plus carboplatin is manageable and induces reasonable response rates in patients with advanced recurrent, platinum-sensitive ovarian cancer. Biomarkers will be collected from both primary tumors and biopsies before and after start of treatment with vorinostat.

DESIGN:Phase II, single-center study. All eligible patients will be treated with intravenous paclitaxel plus carboplatin plus oral vorinostat. Patients will be treated with a maximum of 6 cycles or until disease progression, unacceptable toxicity or withdrawal of consent. Clinical endpoints will include adverse experiences, progression-free survival (PFS) and response rate (RR). SAMPLE:Patients must have a histologically confirmed diagnosis of epithelial ovarian cancer, cancer of the Fallopian tube or primary peritoneal adenocarcinoma. All patients will have received first-line therapy with carboplatin plus paclitaxel. Patients should be platinum sensitive, defined as recurrence or progression of ovarian cancer, cancer of the Fallopian tubes or primary peritoneal adenocarcinoma 6 months or later after the end of first-line chemotherapy. Patients to be enrolled on this study must have acceptable performance status and acceptable renal and hepatic function, and be free of other serious intercurrent illness that could impair their ability to receive protocol therapy. The study will include up to 55 assessable patients, of which 20 will provide biomarkers. It is estimated that the inclusion period will last approximately 24 months. DOSAGE/DOSAGE FORM, ROUTE, AND DOSE REGIMEN Eligible patients will be treated with paclitaxel (175 mg/m2) and carboplatin AUC5 administered by intravenous infusion (IV) on day 1 of each treatment cycle. In addition, all eligible patients will receive treatment with oral vorinostat (400 mg) administered once daily by mouth with food on days -4 through 10 of Cycle 1 (25-day treatment cycle) and days 1 through 14 of each subsequent 21-day treatment cycle. Patients will receive antiemetic therapy according to institutional guidelines as well as premedication with dexamethasone, and antihistamines (an H1-receptor antagonist and an H2-receptor antagonist) for prevention of the side effects of paclitaxel.

Clinical Trial Description

n/a

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

• NCT number: NCT00772798
• Study type: Interventional
• Source: Herlev Hospital
• Contact: Jørn Herrstedt, professor
• Phone: +45 6541 3634
• Email: herrstedt@ouh.regionsyddanmark.dk
• Status: Recruiting
• Phase: Phase 2
• Start date: June 2007
• Completion date: June 2009