A Phase I/II Study of Paclitaxel Plus Carboplatin Plus Vorinostat in Recurrent Ovarian Cancer
Information source: Herlev Hospital
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Ovarian Cancer
Intervention: Paclitaxel, Carboplatin and Vorinostat (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Herlev Hospital Official(s) and/or principal investigator(s):
Jørn Herrstedt, professor, Principal Investigator, Affiliation: Odense University Hospital
Jørn Herrstedt, professor, Principal Investigator, Affiliation: Odense University Hospital
Overall contact:
Jørn Herrstedt, professor, Phone: +45 6541 3634, Email: herrstedt@ouh.regionsyddanmark.dk
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 Details
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
Study design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Primary outcome: Primary:
To assess the objective response rate, safety, tolerability, and adverse experience profile of vorinostat administered in combination with paclitaxel plus carboplatin in patients with platin sensitive recurrent epithelial ovarian cancer.
Secondary outcome: To determine the progression-free survival (PFS) of patients with advanced, recurrent epithelial ovarian cancer, cancer of the Fallopian tube or primary peritoneal adenocarcinoma treated with paclitaxel plus carboplatin and vorinostat.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria:
1. Histological verified epithelial carcinoma derived from ovarian, peritoneum or
uterine tubes
2. Women ≥18 years old.
3. ECOG performance status ≤2.
4. Expected duration of life >3 months.
5. Previous treatment regimen containing platinum and paclitaxel.
6. Platinum and paclitaxel sensitive tumor, defined as a minimum of 6 months from
cessation of treatment until disease progression.
7. Measurable or assessable lesion. Patients having increased CA-125 as the only sign of
recurrence are also eligible.
8. Normal organ functions defined by the following values:
Absolute neutrophil count (ANC) ≥1,500/µL Platelets ≥100,000/µL Hemoglobin ≥9. 0g/dL
or > 5. 7 mmol/L CA125 0-35 Glomerular filtration rate (GFR) measured using Cr-EDTA
clearance GFR ≥50 mL/minute (not corrected for body surface area) Serum Total
bilirubin ≤1. 5 times the ULN AST (SGOT) and ALT (SGPT) ≤2. 5 times the ULN Alkaline
phosphatase ≤5. 0 times the ULN Prothrombin time (PT) ≤1. 2 times the ULN unless the
patient is receiving therapeutic anticoagulation.
Partial thromboplastin time (PTT) ≤1. 2 times the ULN unless the patient is receiving
therapeutic anticoagulation.
9. Signed informed consent before inclusion.
10. Prepared to appear for the planned follow-up visits and capable of handling toxicity.
Exclusion Criteria:
1. Patients treated with an experimental drug within the last 4 weeks before inclusion,
and patients who receive other concomitant anticancer treatment.
2. Patients having an active infection, or who have received intravenous antibacterial
or antifungal medicine within the last 2 weeks before inclusion.
3. Patients previously treated with an HDAC inhibitor. Patients, who have been treated
with Valproate for convulsions can be included, however only if the treatment has
taken place > 30 days before inclusion.
4. Patients treated with steroid, who are not stabilized on a firm dose equivalent to a
maximum of 10 mg prednisolone per day for the last 4 weeks before inclusion.
5. Previous treatment with more than first-line chemotherapy.
6. Progression during treatment with first-line chemotherapy containing
platin/paclitaxel or disease progression less than 6 months after treatment
cessation.
7. Concomitant serious and/or non-controllable medical condition such as
non-controllable infection (including HIV infected patients), hypertension, ischemic
heart disease, myocardial infarction within the last 6 months, congestive heart
failure.
8. Previous treatment for, or other concomitant malignant disease within the last 5
years, except for curative treated carcinoma in situ cervical cancer or basal cell
carcinoma.
9. Previous severe allergic reactions in connection with carboplatin, paclitaxel or
agents within the histone deacetylase inhibitor group.
10. Women of child-bearing age. Women must have undergone surgical removal of the ovaries
or be post-menopausal with no menstruation during the previous year.
11. Peripheral neuropathy ≥ grade 2, unless this is due to a medical condition.
12. Patients with history of severe hyper sensitive reactions with regards to products
containing Cremophor EL (cyclosporine or K-vitamin) and/or patients with known
hypersensitivity towards agents chemically connected to paclitaxel, carboplatin or
vorinostat.
13. Patients with known cerebral metastases or clinical signs of cerebral metastases.
Locations and Contacts
Jørn Herrstedt, professor, Phone: +45 6541 3634, Email: herrstedt@ouh.regionsyddanmark.dk
Department of Oncology R, Odense DK-5000 C, Denmark; Recruiting
Additional Information
Starting date: June 2007
Ending date: June 2009
Last updated: October 14, 2008
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