A Phase I/II Non-Comparative Study of Paclitaxel Plus Carboplatin in Combination With Vorinostat in Patient With Advanced, Recurrent, Epithelial Ovarian Cancer
1. Histological verified epithelial carcinoma derived from ovarian, peritoneum or
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
9. Signed informed consent before inclusion.
10. Prepared to appear for the planned follow-up visits and capable of handling toxicity.
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
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
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
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
13. Patients with known cerebral metastases or clinical signs of cerebral metastases.