A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas

This study has been completed.
Sponsor:
Collaborator:
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
Onxeo
ClinicalTrials.gov Identifier:
NCT00878800
First received: April 7, 2009
Last updated: July 7, 2015
Last verified: July 2015
  Purpose

Open-label, multicentre, dose-escalation Phase I/II study to evaluate safety, efficacy, pharmacodynamics, and pharmacokinetics of the combination of PXD101 with doxorubicin administered q 3 weeks in patients with advanced solid tumours. Once the Maximum Tolerable Dose has been established, up to a total of 20-40 patients with Soft Tissue Sarcoma may be enrolled at the MTD dose level to examine efficacy and safety in this specific patient population. The trial is stopped if no more than 2 responses are seen among the first 20 of these patients.


Condition Intervention Phase
Dose Escalation: Solid Tumors
MTD: Soft Tissue Sarcomas
Drug: PXD101
Drug: Doxorubicin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Onxeo:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) PXD101 [ Time Frame: During Cohort 1 to 4, Cycle 1 only, up to 3 weeks ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Maximum Tolerated Dose (MTD) of doxorubicin

  • Dose Limiting Toxicity (DLT) [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
    Dose Limiting Toxicity (DLT) of PXD101 and doxorubicin combination treatment

  • Objective Response (CR and PR) [ Time Frame: Throughout study, after every 2 cycles ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to Response [ Time Frame: Throughout study, after every 2 cycles ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: Throughout study, after every 2 cycles ] [ Designated as safety issue: No ]
  • Time to Progression [ Time Frame: Throughout study, after every 2 cycles ] [ Designated as safety issue: No ]
  • Disease Control Rate (CR or PR or SD) [ Time Frame: Throughout study, after every 2 cycles ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Enrollment: 41
Study Start Date: December 2006
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed consent of an IEC (Independent Ethics Committee)-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 ≥ 18 years
  6. Acceptable liver, renal and bone marrow function including the following:

    1. Bilirubin ≤ 1.5 times upper limit of normal (ULN)
    2. 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)
    3. Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
    4. Leucocytes > 2.5 x 109/ L, neutrophils > 1.0 x 109/L, platelets > 100 x 109/L
    5. Haemoglobin > 9.0 g/dL or > 5.6 mmol/l
  7. 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.
  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

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 ([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.
  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 ([left ventricular ejection fraction]) 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00878800

Locations
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
Sponsors and Collaborators
Onxeo
Spectrum Pharmaceuticals, Inc
Investigators
Study Director: e-mail contact via enquires@topotarget.com Onxeo
  More Information

No publications provided

Responsible Party: Onxeo
ClinicalTrials.gov Identifier: NCT00878800     History of Changes
Other Study ID Numbers: PXD101-CLN-14
Study First Received: April 7, 2009
Results First Received: July 7, 2014
Last Updated: July 7, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Onxeo:
Phase I/II trial
Solid tumors
Soft tissue sarcoma
PXD101
Doxorubicin

Additional relevant MeSH terms:
Sarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Belinostat
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on July 27, 2015