Dose Escalation: Solid TumorsPhase 1/2NCT00878800
A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas
A Phase 1/2 study testing PXD101 and Doxorubicin in people with Dose Escalation: Solid Tumors and MTD: Soft Tissue Sarcomas, run by Valerio Therapeutics at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dose Escalation: Solid Tumors, MTD: Soft Tissue Sarcomas
- What is being tested?
- PXD101 and Doxorubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Dec 2006to Oct 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Denmark2 sites
Århus Hospital, Department of Oncology
Aarhus, DK-8000 C
Herlev Hospital, Department of Oncology
Herlev, DK-2730
United Kingdom1 site
The Royal Marsden NHS Trust, Cancer Research
Surrey, SM2 5PT Surrey
About this study
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.
- Being tested
- PXD101, Doxorubicin
- Keywords
- Phase I/II trial, Solid tumors, Soft tissue sarcoma, PXD101, Doxorubicin
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PXD101Drug
Also called PXD101 (Belinostat)
Administered in combination with doxorubicin (BelDox)
DoxorubicinDrug
Also called Doxorubicin (Adriamycin)
Administered in combination with PXD101 (BelDox)
| Study group | Role | What they receive |
|---|---|---|
| Experimental: PXD101 and doxorubicin (BelDox) | Experimental | 5-day PXD101 IV schedule with dose escalation combined with 1 day doxorubicin dose escalation IV Receives: Drug: PXD101; Drug: Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) PXD101
Maximum Tolerated Dose (MTD) of PXD101treatment
Measured: During Cohort 1 to 4, Cycle 1 only, up to 3 weeks
Maximum Tolerated Dose (MTD) of Doxorubicin
Maximum Tolerated Dose (MTD) of doxorubicin
Measured: During Cohort 1 to 4, Cycle 1 only, up to 3 weeks
Dose Limiting Toxicity (DLT)
Dose Limiting Toxicity (DLT) of PXD101 and doxorubicin combination treatment
Measured: Throughout study
Objective Response (CR and PR)
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.
Measured: Throughout study, after every 2 cycles
Secondary outcomes (7)
Time to Response
Measured: Throughout study, after every 2 cycles
Duration of Response
Measured: Throughout study, after every 2 cycles
Time to Progression
Measured: Throughout study, after every 2 cycles
Disease Control Rate (CR or PR or SD)
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
Measured: Throughout study, after every 2 cycles
Belinostat AUC (Time 0 to Last Measurement)
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
Measured: 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
Belinostat Cmax
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
Measured: 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
Belinostat t½
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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2009 (estimated)
- Study startDec 2006
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Dose Escalation: Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Valerio Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Spectrum Pharmaceuticals, Inc
- Responsible party
- Sponsor
- Investigators
- e-mail contact via enquires@topotarget.com, Study director, Valerio Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00878800
- Sponsor's protocol ID
- PXD101-CLN-14
- Status last verified
- Jul 2015
- First submitted
- 7 Apr 2009
- Last updated
- 28 Jul 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas
- ClinicalTrials.gov ID
- NCT00878800
- Acronym / sponsor ID
- PXD101-CLN-14
- Keywords
- Phase I/II trial, Solid tumors, Soft tissue sarcoma, PXD101, Doxorubicin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Valerio TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Spectrum Pharmaceuticals, Inc
- Study start
- Dec 2006
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 9 Apr 2009 (estimated)
- Results
- Posted 29 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: PXD101 and doxorubicin (BelDox) | Experimental | Drug: PXD101, Drug: Doxorubicin5-day PXD101 IV schedule with dose escalation combined with 1 day doxorubicin dose escalation IV |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PXD101Also: PXD101 (Belinostat)Administered in combination with doxorubicin (BelDox) | Drug | Experimental: PXD101 and doxorubicin (BelDox) |
| DoxorubicinAlso: Doxorubicin (Adriamycin)Administered in combination with PXD101 (BelDox) | Drug | Experimental: PXD101 and doxorubicin (BelDox) |
Primary outcome
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.
7 secondary outcomes
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
e-mail contact via enquires@topotarget.com study director
Valerio Therapeutics
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PXD101 and Doxorubicin in people with Dose Escalation: Solid Tumors and MTD: Soft Tissue Sarcomas, run by Valerio Therapeutics at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Denmark, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) PXD101 (time frame: During Cohort 1 to 4, Cycle 1 only, up to 3 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2015.