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

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ClinicalTrials.gov Identifier: NCT00878800
Recruitment Status : Completed
First Posted : April 9, 2009
Results First Posted : December 29, 2014
Last Update Posted : July 28, 2015
Sponsor:
Collaborator:
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
Onxeo

Tracking Information
First Submitted Date  ICMJE April 7, 2009
First Posted Date  ICMJE April 9, 2009
Results First Submitted Date  ICMJE July 7, 2014
Results First Posted Date  ICMJE December 29, 2014
Last Update Posted Date July 28, 2015
Study Start Date  ICMJE December 2006
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 17, 2014)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 8, 2009)
Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT)) and efficacy of PXD101 and doxorubicin combination treatment measured by response rate using the RECIST response criteria. [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2014)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2009)
The time to response, duration of response, and survival following PXD101 combination therapy disease control rate (CR+PR+SD) PK of PXD101 and doxorubicin in the combination PD aspects of the treatment [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas
Official Title  ICMJE A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Dose Escalation: Solid Tumors
  • MTD: Soft Tissue Sarcomas
Intervention  ICMJE
  • Drug: PXD101
    Administered in combination with doxorubicin (BelDox)
    Other Name: PXD101 (Belinostat)
  • Drug: Doxorubicin
    Administered in combination with PXD101 (BelDox)
    Other Name: Doxorubicin (Adriamycin)
Study Arms  ICMJE Experimental: Experimental: PXD101 and doxorubicin (BelDox)
5-day PXD101 IV schedule with dose escalation combined with 1 day doxorubicin dose escalation IV
Interventions:
  • Drug: PXD101
  • Drug: Doxorubicin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 17, 2014)
41
Original Estimated Enrollment  ICMJE
 (submitted: April 8, 2009)
65
Actual Study Completion Date  ICMJE October 2012
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00878800
Other Study ID Numbers  ICMJE PXD101-CLN-14
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Onxeo
Study Sponsor  ICMJE Onxeo
Collaborators  ICMJE Spectrum Pharmaceuticals, Inc
Investigators  ICMJE
Study Director: e-mail contact via enquires@topotarget.com Onxeo
PRS Account Onxeo
Verification Date July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP