Ovarian CancerPhase 1/2NCT00421889
A Study of Belinostat + Carboplatin or Paclitaxel or Both in Patients With Ovarian Cancer in Need of Relapse Treatment
A Phase 1/2 study testing belinostat, Paclitaxel and Carboplatin in people with Ovarian Cancer and Epithelial Ovarian Cancer, run by Valerio Therapeutics at 11 sites in 3 countries.
Trial summary
The study seeks to assess the safety, pharmacodynamics, pharmacokinetics and efficacy of belinostat (PXD101) administered in combination with carboplatin or paclitaxel or both in patients with solid tumours followed by maximum tolerated dose (MTD) expansion (phase II) in ovarian and bladder cancer patients The… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer, Epithelial Ovarian Cancer, Fallopian Tube Cancer
- What is being tested?
- belinostat, Paclitaxel and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 11 sitesin 3 countries
- Study dates
- Aug 2005to Feb 2009
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed consent of an IRB (Institutional Review Board) approved consent form.
- Patients with histologically confirmed solid carcinomas, for which there is no known curative therapy.
- Performance status (Eastern Cooperative Oncology Group [ECOG]) ≤ 2.
- Life expectancy of at least 3 months.
- Age ≥ 18 years.
- Acceptable liver, renal and bone marrow function including the following:
Show all 20Show fewer
- Bilirubin ≤ 1.5 times ULN (upper limit of normal).
- AST/SGOT ([Aspartate Amino Transferase/Serum glutamic oxaloacetic transaminase]), ALT/SGPT ([Alanine Amino Transferase/Serum glutamic pyruvic transaminase]) and alkaline phosphatase ≤ 3 times ULN (if liver metastases are present, then ≤ 5 x ULN is allowed).
- Measured EDTA ([ethylenediaminetetraacetic acid]) renal clearance ≥ 45 mL/min (EU sites). At the US sites calculated creatinine clearance ≥ 45 mL/min using the Jeliffe formula.
- Leukocytes > 2.5×109/L, neutrophils > 1.0x109/L, platelets > 100×109/L.
- Hemoglobin > 9.0 g/dL or > 5.6 mmol/L.
- Acceptable coagulation status: PT-INR([prothrombin-International Normalized Ratio])/APTT([Activated Partial Thromboplastin Time]) ≤ 1.5 × ULN or in the therapeutic range if on anticoagulation therapy
- 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 (added in protocol Global version 3.0) Additional Eligibility Criteria at the MTD Expansion only
- Patients with epithelial ovarian cancer in need of relapse treatment. Changed with protocol Global version 3 to: Patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian tumors of ovarian origin in need of relapse treatment.
- Or
- Patients with urothelial (transitional cell) carcinoma of the bladder who have received up to a maximum of 3 previous chemotherapy regimens in the advanced disease setting (neoadjuvant chemotherapy is not included in the total of chemotherapy regimens), applies only for patients enrolled in Part D.
- At least one uni-dimensional measurable lesion. Lesions must be measured by CT scan or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST)(Added with protocol Global version 4).
- Eligibility Criteria for the Site Specific Amendment (Part C) - Advanced solid tumors only
- Patients with refractory solid tumors other than ovarian cancer.
Who cannot join
- Treatment with investigational agents within the last 4 weeks.
- Prior anticancer therapy within the last 3 weeks of study dosing including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents. Changed with protocol Global version 1; prior anticancer therapy within the last 3 weeks of study dosing including chemotherapy, radiotherapy, endocrine therapy or immunotherapy.
- Co-existing active infection or any co-existing medical condition likely to interfere with study 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 ([corrected QT interval ]) > 500 msec; Long QT Syndrome; the required use of concomitant medication on belinostat infusion days that may cause Torsade de Pointes (see Appendix 1.1, protocol EU version 1.0, Appendix A - Appendix 16.1.1).
- Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.
- History of a concurrent second malignancy. Changed with Site Specific Amendment (Part D) to: History of a concurrent second malignancy. In patients with urothelial (transitional cell) carcinoma of the bladder an exception is that an incidental finding of localized prostate cancer at the time of radical cystectomy does not preclude inclusion in the study. In such cases a patient will be eligible for inclusion if the Gleason score is ≤6 and the Prostate Specific Antigen (PSA) <10 ng/mL (if the patient would be on hormonal treatment the PSA must be undetectable).Only applied to patients included in this site specific amendment.
- History of hypersensitivity to either platinum or paclitaxel that is unable to be desensitized (added with protocol Global version 4).
Show all 13Show fewer
- More than 3 prior lines of chemotherapy given for metastatic disease (added with protocol Global version 1).
- Bowel obstruction or impending bowel obstruction.
- Known HIV positivity.
- Any Grade 2 or above drug-related neurotoxicity, following recovery.
- Changed with protocol Global version 1 to: Any existing Grade 2 or above drug related neurotoxicity due to prior treatment with agents causing neurotoxicity.
- Additional exclusion criteria at the MTD expansion only
- Mixed mullerian tumors of intra-uterine origin, added with protocol Global version 3.
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States7 sites
Greater Baltimore Medical Center
Baltimore, Maryland, 21204
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Hematology and Oncology Specialists, LLC
Covington, Louisiana, 70433
Hematology & Oncology Specialists, LLC
Metairie, Louisiana, 70006
Gynecologic Oncology Associates
Newport Beach, California, 92663
Research Facility
Orlando, Florida, 32804
Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
Denmark2 sites
The Finsen Center, Rigshospitalet
Copenhagen, 2100
Research Facility, Herlev University Hospital
Herlev, 2730
United Kingdom2 sites
The Beatson West of Scotland Cancer Centre
Glasgow, G120YN
The Royal Marsden NHS Trust
Surrey, SM2 5PT
About this study
Official title: A Phase I/II Safety, Pharmacodynamic, and Pharmacokinetic Study of Intravenously Administered PXD101 Plus Carboplatin or Paclitaxel or Both in Patients With Advanced Solid Tumours
The study seeks to assess the safety, pharmacodynamics, pharmacokinetics and efficacy of belinostat (PXD101) administered in combination with carboplatin or paclitaxel or both in patients with solid tumours followed by maximum tolerated dose (MTD) expansion (phase II) in ovarian and bladder cancer patients
The clinical trial is now in the MTD (phase II) portion of the study enrolling bladder cancer patients. Enrollment of ovarian patients is complete.
Read the detailed description
MTD Expansion I(Phase II): A total of 18-32 patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian tumours of ovarian origin, in need of relapse treatment will be enrolled.
MTD Expansion II (phase II): A total of 15 patients with urothelial (transitional cell) carcinoma of the bladder will be enrolled.
- Being tested
- belinostat, Paclitaxel, Carboplatin
- Keywords
- Ovarian cancer, Ovarian Neoplasms, Primary peritoneal, Epithelial ovarian, Fallopian tube, Bladder cancer, belinostat, PXD101, mixed mullerian cancer of ovarian origin
- Medical subject headings
- Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
belinostatDrug
Also called PXD101
PaclitaxelDrug
CarboplatinDrug
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Belinostat: 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: Administered IV 2-3 hours after belinostat infusion on day 3 in a 21-day cycle
Carboplatin: Administered IV infusion after paclitaxel on day 3 in a 21-day cycle Receives: Drug: belinostat; Drug: Paclitaxel; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerable Dose (MTD) Belinostat, Part A,
To determine the maximum tolerated dose of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin (AUC of 5) and paclitaxel (175 mg/m2).
Measured: Cycle 1
Dose Limiting Toxicities (DLT), Part A
To determine the number of participants experiencing dose limiting toxicities of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin and paclitaxel or both.
Measured: Cycle 1
Secondary outcomes (8)
Best Overall Response (CR or PR)
Best overall responses were assessed by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Clinical tumor evaluation will take place after each cycle. Formal radiological evaluation after every 2 cycles. If a response is noted, a follow-up radiographic assessment must be performed 4 weeks (+ 1 week) after the response is noted
Measured: Throughout study until PD (progressive disease) or lost to follow up
To Determine the Pharmacodynamic Effects of Belinostat (in the Combination) on Histone Acetylation in Peripheral Blood Mononuclear Cells (Selected Sites)
Measured: Throughout the study
Time to Progression
Time to progression, defined as the interval between the first dates of treatment until the first notation of disease progression. RECIST criteria
Measured: Throughout study
Time to Response
Time to response (RECIST) was assessed as the interval between the first dates of treatment until the first notation of response.
Measured: Throughout study
Duration of Response
Defined as interval from the time criteria for CR or PR are met, until the first date that recurrent or progressive disease is objectively documented.
Measured: Throughout study
Belinostat Cmax
Measured: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h
Belinostat Mean t½
Measured: Cycle 1 Day 1: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h
Belinostat AUC (0-infinity)
Measured: Cycle 1 Day 1: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2007 (estimated)
- Study startAug 2005
- Primary completionFeb 2009
- Study completionFeb 2009
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 Ovarian CancerStudies 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
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Valerio Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- e-mail contact via enquires@topotarget.com, Study director, Valerio Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00421889
- Sponsor's protocol ID
- PXD101-CLN-8
- Other IDs
- PXD101-040-EU
- Status last verified
- Jul 2015
- First submitted
- 12 Jan 2007
- Last updated
- 28 Jul 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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 Safety, Pharmacodynamic, and Pharmacokinetic Study of Intravenously Administered PXD101 Plus Carboplatin or Paclitaxel or Both in Patients With Advanced Solid Tumours
- ClinicalTrials.gov ID
- NCT00421889
- Acronym / sponsor ID
- PXD101-CLN-8
- Keywords
- Ovarian cancer, Ovarian Neoplasms, Primary peritoneal, Epithelial ovarian, Fallopian tube, Bladder cancer, belinostat, PXD101
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Valerio TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Aug 2005
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 15 Jan 2007 (estimated)
- Results
- Posted 15 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study seeks to assess the safety, pharmacodynamics, pharmacokinetics and efficacy of belinostat (PXD101) administered in combination with carboplatin or paclitaxel or both in patients with solid tumours followed by maximum tolerated dose (MTD) expansion (phase II) in ovarian and bladder cancer patients
The clinical trial is now in the MTD (phase II) portion of the study enrolling bladder cancer patients. Enrollment of ovarian patients is complete.
Detailed description
MTD Expansion I(Phase II): A total of 18-32 patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian tumours of ovarian origin, in need of relapse treatment will be enrolled.
MTD Expansion II (phase II): A total of 15 patients with urothelial (transitional cell) carcinoma of the bladder will be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: belinostat, Drug: Paclitaxel, Drug: CarboplatinBelinostat: 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: Administered IV 2-3 hours after belinostat infusion on day 3 in a 21-day cycle Carboplatin: Administered IV infusion after paclitaxel on day 3 in a 21-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Signed consent of an IRB (Institutional Review Board) approved consent form.
- Patients with histologically confirmed solid carcinomas, for which there is no known curative therapy.
- Performance status (Eastern Cooperative Oncology Group [ECOG]) ≤ 2.
- Life expectancy of at least 3 months.
- Age ≥ 18 years.
Key exclusion criteria (13 listed)
- Treatment with investigational agents within the last 4 weeks.
- Prior anticancer therapy within the last 3 weeks of study dosing including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents. Changed with protocol Global version 1; prior anticancer therapy within the last 3 weeks of study dosing including chemotherapy, radiotherapy, endocrine therapy or immunotherapy.
- Co-existing active infection or any co-existing medical condition likely to interfere with study 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 ([corrected QT interval ]) > 500 msec; Long QT Syndrome; the required use of concomitant medication on belinostat infusion days that may cause Torsade de Pointes (see Appendix 1.1, protocol EU version 1.0, Appendix A - Appendix 16.1.1).
- Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.
- History of a concurrent second malignancy. Changed with Site Specific Amendment (Part D) to: History of a concurrent second malignancy. In patients with urothelial (transitional cell) carcinoma of the bladder an exception is that an incidental finding of localized prostate cancer at the time of radical cystectomy does not preclude inclusion in the study. In such cases a patient will be eligible for inclusion if the Gleason score is ≤6 and the Prostate Specific Antigen (PSA) <10 ng/mL (if the patient would be on hormonal treatment the PSA must be undetectable).Only applied to patients included in this site specific amendment.
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 |
|---|---|---|
| belinostatAlso: PXD101 | Drug | Single arm |
| Paclitaxel | Drug | Single arm |
| Carboplatin | Drug | Single arm |
Primary outcome
Maximum Tolerable Dose (MTD) Belinostat, Part A,
Time frame: Cycle 1
To determine the maximum tolerated dose of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin (AUC of 5) and paclitaxel (175 mg/m2).
Dose Limiting Toxicities (DLT), Part A
Time frame: Cycle 1
To determine the number of participants experiencing dose limiting toxicities of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin and paclitaxel or both.
8 secondary outcomes
Best Overall Response (CR or PR)
Time frame: Throughout study until PD (progressive disease) or lost to follow up
To Determine the Pharmacodynamic Effects of Belinostat (in the Combination) on Histone Acetylation in Peripheral Blood Mononuclear Cells (Selected Sites)
Time frame: Throughout the study
Time to Progression
Time frame: Throughout study
Time to Response
Time frame: Throughout study
Duration of Response
Time frame: Throughout study
Belinostat Cmax
Time frame: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h
Belinostat Mean t½
Time frame: Cycle 1 Day 1: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h
Belinostat AUC (0-infinity)
Time frame: Cycle 1 Day 1: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h
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.
Related trials for Ovarian Cancer
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Recruiting
A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer
Ovarian Carcinoma
RecruitingPhase 2
Investigation of Ubamatamab Combination Therapy in Adult Participants With Platinum-Resistant Ovarian Cancer
Ovarian Cancer, Fallopian Tube Cancer
Active, not recruitingPhase 1/2
Phase I/II Study of the Anti-Programmed Death Ligand-1 Durvalumab Antibody (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Can...
Colorectal Neoplasms, Breast Neoplasms
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
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
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing belinostat, Paclitaxel and Carboplatin in people with Ovarian Cancer and Epithelial Ovarian Cancer, run by Valerio Therapeutics at 11 sites in 3 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 20 inclusion and 13 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 11 sites in United States, 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 15 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 Tolerable Dose (MTD) Belinostat, Part A, (time frame: Cycle 1). The study lists 2 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.