A Phase I/II Study of Paclitaxel Plus Carboplatin Plus Vorinostat in Recurrent Ovarian Cancer
Status:
Unknown status
Trial end date:
2009-06-01
Target enrollment:
Participant gender:
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.