Brief Title
A Study of Belinostat + Carboplatin or Paclitaxel or Both in Patients With Ovarian Cancer in Need of Relapse Treatment
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
Brief 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 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 Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Maximum Tolerable Dose (MTD) Belinostat, Part A,
Secondary Outcome
Best Overall Response (CR or PR)
Condition
Ovarian Cancer
Intervention
belinostat
Study Arms / Comparison Groups
Single arm
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
80
Start Date
August 2005
Completion Date
February 2009
Primary Completion Date
February 2009
Eligibility Criteria
Inclusion Criteria:
1. Signed consent of an IRB (Institutional Review Board) approved consent form.
2. Patients with histologically confirmed solid carcinomas, for which there is no known
curative therapy.
3. Performance status (Eastern Cooperative Oncology Group [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 ULN (upper limit of normal).
2. 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).
3. 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.
4. Leukocytes > 2.5×109/L, neutrophils > 1.0x109/L, platelets > 100×109/L.
5. Hemoglobin > 9.0 g/dL or > 5.6 mmol/L.
7. 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
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 (added in protocol Global version 3.0) Additional
Eligibility Criteria at the MTD Expansion only
10. 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
11. 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.
12. 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
13. Patients with refractory solid tumors other than ovarian cancer.
Exclusion Criteria:
1. Treatment with investigational agents within the last 4 weeks.
2. 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.
3. 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).
4. Altered mental status precluding understanding of the informed consent process and/or
completion of the necessary studies.
5. 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.
6. History of hypersensitivity to either platinum or paclitaxel that is unable to be
desensitized (added with protocol Global version 4).
7. More than 3 prior lines of chemotherapy given for metastatic disease (added with
protocol Global version 1).
8. Bowel obstruction or impending bowel obstruction.
9. Known HIV positivity.
10. Any Grade 2 or above drug-related neurotoxicity, following recovery.
11. 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
12. Mixed mullerian tumors of intra-uterine origin, added with protocol Global version 3.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
e-mail contact via [email protected], ,
Location Countries
Denmark
Location Countries
Denmark
Administrative Informations
NCT ID
NCT00421889
Organization ID
PXD101-CLN-8
Secondary IDs
PXD101-040-EU
Responsible Party
Sponsor
Study Sponsor
Onxeo
Study Sponsor
e-mail contact via [email protected], Study Director, Onxeo
Verification Date
July 2015