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

This is an interventional treatment trial for Ovarian Cancer focused on measuring ovarian cancer, HDAC inhibitor, vorinostat Read More

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.