Brief Title
PXD101 and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas
Official Title
A Phase 1 Study of PXD101 in Combination With Bortezomib (PS-341) in Patients With Advanced Solid Tumors and Lymphoma
Brief Summary
This phase I trial is studying the side effects and best dose of PXD101 and bortezomib in
treating patients with advanced solid tumors or lymphomas. PXD101 and bortezomib may stop the
growth of cancer cells by blocking some of the enzymes needed for cell growth. PXD101 may
also cause cancer cells to look more like normal cells, and to grow and spread more slowly.
Giving PXD101 together with bortezomib may kill more cancer cells.
Detailed Description
OBJECTIVES:
I. Evaluate the safety profile and determine the maximum tolerated dose of PXD101 in
combination with bortezomib in patients with advanced solid tumors or lymphomas.
II. Determine the pharmacokinetics of the combination of PXD101 and bortezomib in these
patients.
III. Evaluate selected biomarkers of drug effect in these patients. IV. Evaluate the activity
of this regimen, in terms of objective response rate, in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive PXD101 IV over 30 minutes on days 1-5 and bortezomib IV on days 1, 4, 8, and
11 (2, 5, 8, and 11 during course 1). Treatment repeats every 21 days in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-9 patients receive escalating doses of bortezomib and PXD101 until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 6 patients experience dose-limiting toxicity. Blood is collected at baseline and
periodically during course 1 of study treatment for pharmacokinetic studies.
After completion of study treatment, patients are followed periodically for 4 weeks.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum tolerated dose of PXD101 in combination with bortezomib
Secondary Outcome
Pharmacokinetics of the combination of PXD101 with bortezomib
Condition
Adult Grade III Lymphomatoid Granulomatosis
Intervention
belinostat
Study Arms / Comparison Groups
PXD101 in Combination with Bortezomib (PS-341)
Description: Patients receive PXD101 IV over 30 minutes on days 1-5 and bortezomib IV on days 1, 4, 8, and 11 (2, 5, 8, and 11 during course 1).
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
55
Start Date
March 2006
Primary Completion Date
January 2010
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed solid tumor or lymphoma that is refractory
to standard therapy or for which no standard therapy exists
- No active, untreated, or symptomatic brain metastases
- Patients with treated brain metastases are eligible provided metastasis are
stable and the patient is off all steroids and anticonvulsants
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 1.5 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of
liver metastases)
- Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to PXD101, bortezomib, boron, or mannitol
- No peripheral neuropathy > grade 1
- No uncontrolled intercurrent illness, including, but not limited to, any of the
following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Psychiatric illness or social situation that would preclude study requirements
- No significant cardiovascular disease, including any of the following:
- Myocardial infarction within the past 6 months
- New York Heart Association class III-IV heart failure
- Unstable angina pectoris
- Uncontrolled hypertension
- Condition requiring antiarrhythmic therapy
- Ischemic or severe valvular heart disease
- Acute ischemia or active conduction system abnormalities by ECG
- No marked baseline prolongation of QT/QTc interval (repeated demonstration of a QTc
interval > 500 msec), long QT syndrome, or required use of concurrent medication
during PXD101 administration that may cause torsade de pointes
- No severe medical or psychiatric problems of that would preclude study compliance
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, carmustine, or
mitomycin C)
- At least 4 weeks since prior radiotherapy and recovered
- At least 2 weeks since prior palliative radiotherapy to sites involving < 35% of bone
marrow reserve
- At least 4 weeks since prior investigational agents
- At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor
- No prior stem cell or bone marrow transplantation
- No concurrent radiotherapy or immunotherapy
- No concurrent hormonal therapy
- Luteinizing hormone-releasing hormone agonists, selective estrogen receptor
modulators, or aromatase inhibitors as chronic maintenance therapy allowed
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies
Gender
All
Ages
16 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Sue Eckhardt, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00348985
Organization ID
NCI-2009-01052
Secondary IDs
COMIRB 05-0705
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Sue Eckhardt, Principal Investigator, University of Colorado, Denver
Verification Date
May 2013