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A Phase I Study of PS-341 in Combination With Paclitaxel in Metastatic Solid Tumors

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of PS-341 in Combination With Paclitaxel in Metastatic Solid Tumors


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

- 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:


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:


Principal Investigator

Charles Shapiro

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University


United States: Food and Drug Administration

Study ID:




Start Date:

November 2001

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasms



Ohio State University Medical Center Columbus, Ohio  43210