In the MTD expansion arm only women with a history of epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian tumours of ovarian origin participate to confirm the safety and to examine efficacy in this specific patient population. MedDRA version: 8.1 Level: LLT Classification code 10033128 Term: Ovarian cancer
Conditions
Interventions
Product Code: PXD101
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not available
CAS Number: 414864-00-9
Current Spons
Sponsors
TopoTarget A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed consent of an IRB-approved consent form 2. Patients with histologically or cytologically confirmed solid carcinomas, for which there is no known curative therapy 3. Performance status (ECOG) = 2 4. Life expectancy of at least 3 months 5. Age = 18 years 6. Acceptable liver, renal and bone marrow function including the following: a. Bilirubin = 1.5 times upper limit of normal (ULN) b. AST (SGOT), ALT (SGPT) and Alkaline Phosphatase = 3 times upper limit of normal (if liver metastases are present, then = 5 x ULN is allowed) c. Measured EDTA renal clearance = 45 mL/min (EU sites). At the US sites a calculated creatinine clearance = 45 mL/min using the Jeliffe formula. d. Leucocytes > 2.5 x 109/L, neutrophils > 1.0 x 109/L, platelets > 100 x 109/L e. Hemoglobin > 9.0 g/dL or > 5.6 mmol/l 7. Acceptable coagulation status: PT-INR/PTT = 1.5 x ULN or in the therapeutic range if on anticoagulation therapy 8. A negative pregnancy test for women of childbearing potential. For men and women of child-producing potential, the use of effective contraceptive methods during the study is required. 9. Serum potassium within normal range Additional eligibility criteria at the MTD expansion only 10. Patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian tumours of ovarian origin in need of relapse treatment 11. At least one uni-dimensional measurable lesion. Lesions must be measured by CT-scan or MRI according to RECIST Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Treatment with investigational agents within the last 4 weeks 2. Prior anticancer therapy within the last 3 weeks of trial dosing including chemotherapy, radiotherapy, endocrine therapy or immunotherapy 3. Co-existing active infection or any co-existing medical condition likely to interfere with trial procedures, including significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, congestive heart failure requiring therapy, unstable arrhythmia or a need for anti-arrhythmic therapy, or evidence of ischemia on ECG, marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval > 500 msec; Long QT Syndrome; the required use of concomitant medication on PXD101 infusion days that may cause Torsade de Pointes. (See Appendix A). 4. Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies 5. History of a concurrent second malignancy 6. History of hypersensitivity to either platinum or paclitaxel that is unable to be desentized 7. More than three prior lines of chemotherapy given for metastatic disease 8. Bowel obstruction or impending bowel obstruction 9. Known HIV positivity 10. Any existing grade 2 or above drug-related neurotoxicity due to prior treatment with agents causing neurotoxicity Additional exclusion criteria at the MTD expansion only 11. Mixed mullerian tumours of intra-uterine origin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Following establishment of MTD up to a total of 32 patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian tumours of ovarian origin may be enrolled at the MTD dose level to confirm safety and to examine efficacy in this specific patient population.; Secondary Objective: To determine the pharmacokinetics of PXD101 and its effect on carboplatin and paclitaxel pharmacokinetics. Carboplatin and paclitaxel baselines will be defined from historical and/or literature data. To determine the pharmacodynamic effect of PXD101 in combination with carboplatin and/or paclitaxel on histone acetylation in peripheral mononuclear blood cells (selected sites) To explore anti-tumour activity of the combination of PXD101 plus carboplatin and paclitaxel in patients with advanced solid tumors, and in the MTD expansion arm in patients with ovarian cancer in need of relapse treatment ;Primary end point(s): Documentation of MTD of the 3 drug combination PXD101+paclitaxel+carboplatin | — |
Countries
United Kingdom
Outcome results
None listed