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A Phase I/II Safety, Pharmacodynamic, and Pharmacokinetic Study of Intravenously Administered PXD101 Plus Carboplatin or Paclitaxel or Both in Patients with Advanced Solid Tumours - PXD101-040-EU Global V4

Phase 1
Conditions
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
Registration Number
EUCTR2005-002338-36-GB
Lead Sponsor
TopoTarget A/S
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Not specified
Target Recruitment
65
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

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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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