A. For the dose escalation phase: Patients with histological or cytological confirmed solid tumours (including sarcomas), for which there is no known curative therapy B. For the MTD expansion phase: Patients with an established diagnosis of soft tissue sarcoma in need of first line chemotherapy and with measurable disease MedDRA version: 14.1 Level: PT Classification code 10039491 Term: Sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: PXD101
Product Code: PXD101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Belinostat
CAS Number: 414864-00-9
Current Sponsor code: PXD101
Concentration
Sponsors
Topotarget A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria 1. Signed consent of an IEC-approved Information consent form 2. A. For the dose escalation phase: Patients with histological or cytological confirmed solid tumours (including sarcomas), for which there is no known curative therapy B. For the MTD expansion phase: Patients with an established diagnosis of soft tissue sarcoma in need of first line chemotherapy and with measurable disease 3. Performance status (ECOG) = 2 4. Life expectancy of at least 3 months 5. Age ³ 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. Serum creatinine = 1.5 times upper limit of normal (ULN) d. Leucocytes > 2.5 x 109/L, neutrophils > 1.0 x 109/L, platelets > 100 x 109/L e. Haemoglobin > 9.0 g/dL or > 5.6 mmol/l 7. Acceptable coagulation status: PT and APTT within = 1.5 times upper limit of normal or in the therapeutic range if on anticoagulation. 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 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 27 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
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. Concurrent second malignancy 6. History of hypersensitivity to doxorubicin 7. A. For dose escalation phase: More than two prior doses of anthracycline, more than three prior lines of chemotherapy given for metastatic disease B. For MTD expansion phase: Prior chemotherapy 8. Bowel obstruction or impending bowel obstruction 9. Known HIV positivity 10. LVEF below normal range ( 45% by MUGA) 11. Presence of metastatic disease that, in the opinion of the investigator, would require palliative treatment within 4 weeks of enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1. Determination of MTD 2. Efficacy of the MTD dosed sarcoma patients.;Timepoint(s) of evaluation of this end point: 1. 2011 2. 2013;Main Objective: The primary objective of this trial is to determine the tolerance (Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT)) and efficacy of PXD101 and doxorubicin combination treatment as measured by response rate (CR or PR using the RECIST response criteria). ;Secondary Objective: The secondary objective of the trial is • to examine the time to response, the duration of response, and survival following PXD101 combination therapy. • to examine disease control rate (CR+PR+SD) • to examine the PK of PXD101 and doxorubicin in the combination • to examine PD aspects of the treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • to examine the time to response, the duration of response, and survival following PXD101 combination therapy. • to examine disease control rate (CR+PR+SD) • to examine the PK of PXD101 and doxorubicin in the combination • to examine PD aspects of the treatment ;Timepoint(s) of evaluation of this end point: 2013 | — |
Countries
Denmark, United Kingdom
Contacts
Public ContactClinical Operations
Topotarget A/S
Outcome results
None listed