Phase I Trial of Bortezomib (VELCADE™) and Celecoxib in Patients With Advanced Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Phase I Trial of Bortezomib (VELCADE™) and Celecoxib in Patients With Advanced Solid Tumors
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of bortezomib and celecoxib in patients with
advanced solid tumors.
Secondary
- Determine the overall pattern of toxicities associated with this combination, including
the emergence of any cumulative toxicities, during multiple courses of this regimen.
- Describe the response rate and duration of response or disease stability during therapy
in the subset of patients with measurable disease.
- Assess changes in plasma/serum sphingosine-1-phosphate, ceramide, and other markers of
the apoptotic pathway before and during therapy.
OUTLINE: This is a dose-escalation study.
Patients receive bortezomib IV on days 1, 4, 8, and 11 or days 1, 8, 15, 22, and 29 and oral
celecoxib twice daily on days 1-21 or 1-42. Courses repeat every 21 or 42 days in the
absence of disease progression or unacceptable toxicity. Patients are evaluated every 2
courses. Patients achieving complete response (CR) receive 2 additional courses of therapy
beyond CR.
Cohorts of 3-6 patients receive escalating doses of bortezomib and celecoxib 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.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologic or cytologic diagnosis of a malignant neoplasm (solid tumor) arising from
any primary site with the exception of bone marrow or lymphoid tissue
- Recurrent or progressive disease after chemotherapy or radiotherapy
- Chemotherapy or radiotherapy-naive disease allowed if patient is not a candidate
for standard treatment either due to comorbidities or lack of willingness to
undergo standard treatment
- Measurable disease
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 30 mL/min
- Bilirubin ≤ 2 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active concurrent invasive malignancy
- No peripheral neuropathy ≥ grade 2 within the past 14 days
- No hypersensitivity to bortezomib, boron, mannitol, any of the cyclooxygenase (COX-2)
inhibitors, sulfa drugs, or other nonsteroidal anti-inflammatory drugs (NSAIDs)
- No active gastrointestinal (GI) ulcers OR history of GI bleeding resulting from prior
therapy with NSAIDs
PRIOR CONCURRENT THERAPY:
- At least 2 weeks since completion of prior radiotherapy
- No prior bortezomib
- No other concurrent investigational agents
- No concurrent chemotherapy, radiotherapy, or anticancer surgery
- No concurrent immune-enhancing therapy
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose
Safety Issue:
Yes
Principal Investigator
Andrew S. Kraft, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Medical University of South Carolina
Authority:
United States: Federal Government
Study ID:
CDR0000454922
NCT ID:
NCT00290680
Start Date:
March 2005
Completion Date:
January 2009
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina 29425 |
