A Phase I Study of PS-341 in Combination With Paclitaxel in Metastatic Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of PS-341 in Combination With Paclitaxel in Metastatic Solid Tumors
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of bortezomib when given in combination with
paclitaxel in patients with locally advanced or metastatic solid tumors.
OUTLINE: This is a multicenter, dose-escalation study of bortezomib.
Patients receive bortezomib IV on days 2 and 9 and paclitaxel IV over 1 hour on days 1 and
8. For the first course only, patients do not receive paclitaxel on day 1. Courses repeat
every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity or greater than 80% 20S proteasome
inhibition. Once the MTD is determined, an additional 6-9 patients are accrued and treated
at that dose.
Patients are followed at 21 days.
PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.
Inclusion Criteria:
- Histologically or cytologically confirmed locally advanced or metastatic solid tumor
for which there is no curative treatment
- No known brain metastases
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- WBC at least 3,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin normal
- AST/ALT no greater than 2.5 times upper limit of normal (ULN)
- Creatinine no greater than ULN
- Left ventricular function at least lower limit of normal if received prior
doxorubicin
- No grade II or IV tilt-table test
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No thrombotic event within the past 6 months
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No prior allergic reaction to compounds of similar chemical or biological composition
to study drugs
- No other concurrent uncontrolled illness
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- Prior paclitaxel allowed
- At least 2 weeks since prior hormonal therapy
- No concurrent steroids or hormonal therapy except steroids to prevent
hypersensitivity reactions to paclitaxel or hormonal therapy for non-disease-related
conditions (e.g., insulin for diabetes)
- At least 4 weeks since prior radiotherapy
- At least 4 weeks since prior surgery
- Recovered from prior therapy
- No other concurrent investigational agents
- No concurrent combination anti-retroviral therapy for HIV-positive patients
- No concurrent anticoagulation therapy
- Concurrent pamidronate or zoledronate allowed for treatment of hypercalcemia or for
palliation of skeletal metastases
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Dose-limiting toxicity (DLT) defined as Common Terminology Criteria (CTC) version 2.0 grade 3 or greater non-hematologic toxicity or grade 4 hematologic toxicity with the exception of asymptomatic neutropenia [ANC < 500]
Outcome Time Frame:
21 days
Safety Issue:
Yes
Principal Investigator
Charles Shapiro
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ohio State University
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-01408
NCT ID:
NCT00030368
Start Date:
November 2001
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- Neoplasms
Name | Location |
|---|---|
| Ohio State University Medical Center | Columbus, Ohio 43210 |
