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A Phase 1 Study of PS-341 in Combination With Docetaxel in Patients With Advanced Solid Tumors

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

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Trial Information

A Phase 1 Study of PS-341 in Combination With Docetaxel in Patients With Advanced Solid Tumors


I. Determine the maximum tolerated dose of bortezomib and docetaxel in patients with
advanced solid tumors.

II. Determine the toxicity and tolerability of this regimen in these patients. III.
Determine the biologic correlates of proteasome inhibition of bortezomib and determine the
effects of this inhibition on the pharmacokinetics of docetaxel in these patients.

IV. Determine the antitumor efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

For course 1, patients receive docetaxel IV over 1 hour on days 1 and 8 and bortezomib IV
over 3-5 seconds on days 9 and 12. Patients then receive 1 week of rest. For course 2 and
all subsequent courses, patients receive docetaxel on days 1 and 8 and bortezomib on days 2,
5, 9, and 12. Courses repeat every 3 weeks in the absence of disease progression or
unacceptable toxicity. Cohorts of 2-6 patients receive escalating doses of bortezomib and
docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.

PROJECTED ACCRUAL: A minimum of 24 patients will be accrued for this study.

Inclusion Criteria:

- Histologically confirmed solid tumor for which standard curative or palliative
measures do not exist or are no longer effective

- Metastatic or unresectable disease

- No known brain metastases

- Performance status - ECOG 0-2

- Performance status - Karnofsky 50-100%

- More than 12 weeks

- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 8 g/dL

- Bilirubin normal

- AST and ALT no greater than 1.5 times upper limit of normal (ULN) and alkaline
phosphatase no greater than 2.5 times ULN

- Alkaline phosphatase no greater than 5 times ULN (unless bone-derived) and AST and
ALT less than 1.5 times ULN

- Creatinine normal

- Creatinine clearance at least 60 mL/min

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study

- No prior allergic reactions attributed to taxanes (e.g., docetaxel or paclitaxel) or
compounds of similar chemical or biological composition

- No prior allergic reactions to compounds similar to bortezomib or other study agents

- No known hypersensitivity to corticosteroids

- No predicted intolerance to regular, repeated administration of corticosteroids
(e.g., poorly controlled diabetes or significant osteoporosis/osteopenia)

- No ongoing or active infection

- No other uncontrolled concurrent illness that would preclude study participation

- No psychiatric illness or social situation that would preclude study participation

- No peripheral neuropathy grade 2 or greater

- At least 4 weeks since prior chemotherapy (6 weeks for carmustine, nitrosoureas, or
mitomycin) and recovered

- No more than 3 courses of mitomycin

- Prior taxanes allowed

- At least 6 months since prior docetaxel administered on a weekly schedule

- At least 4 weeks since prior radiotherapy and recovered

- No other concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent anticancer agents or therapies (commercial or investigational)

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by the NCI Common Toxicity Criteria (CTC) version 2.0

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Deborah Armstrong

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins University


United States: Food and Drug Administration

Study ID:




Start Date:

August 2002

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasms



Johns Hopkins University Baltimore, Maryland  21205