A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT00878800 |
Recruitment Status :
Completed
First Posted : April 9, 2009
Results First Posted : December 29, 2014
Last Update Posted : July 28, 2015
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Dose Escalation: Solid Tumors MTD: Soft Tissue Sarcomas | Drug: PXD101 Drug: Doxorubicin | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 41 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas |
Study Start Date : | December 2006 |
Actual Primary Completion Date : | October 2012 |
Actual Study Completion Date : | October 2012 |

Arm | Intervention/treatment |
---|---|
Experimental: Experimental: PXD101 and doxorubicin (BelDox)
5-day PXD101 IV schedule with dose escalation combined with 1 day doxorubicin dose escalation IV
|
Drug: PXD101
Administered in combination with doxorubicin (BelDox)
Other Name: PXD101 (Belinostat) Drug: Doxorubicin Administered in combination with PXD101 (BelDox)
Other Name: Doxorubicin (Adriamycin) |
- Maximum Tolerated Dose (MTD) PXD101 [ Time Frame: During Cohort 1 to 4, Cycle 1 only, up to 3 weeks ]Maximum Tolerated Dose (MTD) of PXD101treatment
- Maximum Tolerated Dose (MTD) of Doxorubicin [ Time Frame: During Cohort 1 to 4, Cycle 1 only, up to 3 weeks ]Maximum Tolerated Dose (MTD) of doxorubicin
- Dose Limiting Toxicity (DLT) [ Time Frame: Throughout study ]Dose Limiting Toxicity (DLT) of PXD101 and doxorubicin combination treatment
- Objective Response (CR and PR) [ Time Frame: Throughout study, after every 2 cycles ]Measured by response rate using the RECIST (Response Evaluation Criteria in Solid Tumors) response criteria (response rate: Complete Response (CR) and Partial Response (PR)) following up to 6 cycles of treatment.
- Time to Response [ Time Frame: Throughout study, after every 2 cycles ]
- Duration of Response [ Time Frame: Throughout study, after every 2 cycles ]
- Time to Progression [ Time Frame: Throughout study, after every 2 cycles ]
- Disease Control Rate (CR or PR or SD) [ Time Frame: Throughout study, after every 2 cycles ]The disease control rate, defined as best overall response of either objective response or stable disease (CR or PR or SD) following up to 6 cycles of treatment with confirmation according to the RECIST criteria
- Belinostat AUC (Time 0 to Last Measurement) [ Time Frame: Cycle 1, Day 4 and Day 5, pre-infusion, at end of infusion and at 5 min, 15 min, 30 min, 1 h, 2 h, 2 h and 15 min, 2 h and 30 min, 3 h, 4 h, 6 h, 8 h and 24 h post infusion ]Measure the AUC of belinostat alone (Day 4 values) and in the presence of doxorubicin (Day 5 values) at the Maximum Tolerated Dose level: belinostat 1000 mg/m2 and doxorubicin 75 mg/m2
- Belinostat Cmax [ Time Frame: Cycle 1, Day 4 and Day 5, pre-infusion, at end of infusion and at 5 min, 15 min, 30 min, 1 h, 2 h, 2 h and 15 min, 2 h and 30 min, 3 h, 4 h, 6 h, 8 h and 24 h post infusion ]Measure the Cmax of belinostat alone (Day 4 values) and in the presence of doxorubicin (Day 5 values) at the Maximum Tolerated Dose level: belinostat 1000 mg/m2 and doxorubicin 75 mg/m2
- Belinostat t½ [ Time Frame: Cycle 1, Day 4 and Day 5, pre-infusion, at end of infusion and at 5 min, 15 min, 30 min, 1 h, 2 h, 2 h and 15 min, 2 h and 30 min, 3 h, 4 h, 6 h, 8 h and 24 h post infusion ]Measure the t½ of belinostat alone (Day 4 values) and in the presence of doxorubicin (Day 5 values) at the Maximum Tolerated Dose level: belinostat 1000 mg/m2 and doxorubicin 75 mg/m2

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Signed consent of an IEC (Independent Ethics Committee)-approved Information consent form
- 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
- Performance status (ECOG) ≤ 2
- Life expectancy of at least 3 months
- Age ≥ 18 years
-
Acceptable liver, renal and bone marrow function including the following:
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST ([Aspartate Amino Transferase]](SGOT), ALT (SGPT) and Alkaline Phosphatase ≤ 3 times upper limit of normal (if liver metastases are present, then ≤ 5 x ULN is allowed)
- Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
- Leucocytes > 2.5 x 109/ L, neutrophils > 1.0 x 109/L, platelets > 100 x 109/L
- Haemoglobin > 9.0 g/dL or > 5.6 mmol/l
- Acceptable coagulation status: PT and APTT ([activated partial thromboplastin time ]) within ≤ 1.5 times upper limit of normal or in the therapeutic range if on anticoagulation.
- 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
- Serum potassium within normal range
Exclusion Criteria:
- Treatment with investigational agents within the last 4 weeks
- Prior anticancer therapy, within the last 3 weeks of trial dosing including chemotherapy, radiotherapy, endocrine therapy or immunotherapy
- 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 ([corrected QT interval ]) 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.
- Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
- Concurrent second malignancy
- History of hypersensitivity to doxorubicin
- 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
- Bowel obstruction or impending bowel obstruction
- Known HIV positivity
- LVEF ([left ventricular ejection fraction]) below normal range (45% by MUGA)
- Presence of metastatic disease that, in the opinion of the investigator, would require palliative treatment within 4 weeks of enrolment

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00878800
Denmark | |
Herlev Hospital, Department of Oncology | |
Herlev, Denmark, DK-2730 | |
Århus Hospital, Department of Oncology | |
Århus, Denmark, DK-8000 C | |
United Kingdom | |
The Royal Marsden NHS Trust, Cancer Research | |
Surrey, United Kingdom, SM2 5PT Surrey |
Study Director: | e-mail contact via enquires@topotarget.com | Onxeo |
Responsible Party: | Onxeo |
ClinicalTrials.gov Identifier: | NCT00878800 |
Other Study ID Numbers: |
PXD101-CLN-14 |
First Posted: | April 9, 2009 Key Record Dates |
Results First Posted: | December 29, 2014 |
Last Update Posted: | July 28, 2015 |
Last Verified: | July 2015 |
Phase I/II trial Solid tumors Soft tissue sarcoma PXD101 Doxorubicin |
Sarcoma Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Doxorubicin Liposomal doxorubicin Belinostat |
Antibiotics, Antineoplastic Antineoplastic Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Histone Deacetylase Inhibitors |