A Phase I Trial of PS-341 in Combination With Topotecan in Advanced Solid Tumor Malignancies
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Trial of PS-341 in Combination With Topotecan in Advanced Solid Tumor Malignancies
PRIMARY OBJECTIVES:
I. To assess the safety and feasibility of combining PS-341 with topotecan in patients with
advanced solid tumor malignancies.
II. To define the maximum tolerated dose (MTD) of topotecan when administered in combination
with a fixed dose of PS-341 and to described the toxicities at each dose studied.
III. To evaluate the pharmacokinetics of topotecan when given in combination with PS-341 at
MTD.
SECONDARY OBJECTIVES:
I. To perform laboratory correlative studies on patients tissue investigating potential
predictors of response.
OUTLINE:
PART I (completed as of 09/06/06; all patients enrolled in study after 09/06/06 are enrolled
in part II): Patients receive escalating doses of topotecan hydrochloride IV over 30 minutes
on days 1 and 8 followed 6 hours later by bortezomib IV on days 1, 4, 8, and 11. Treatment
repeats every 21 days for at least 4 courses in the absence of disease progression or
unacceptable toxicity.
PART II: Patients receive bortezomib IV on days 1, 4, 8, and 11 followed 6 hours later by
escalating doses of topotecan hydrochloride IV over 30 minutes on days 1 and 8. Treatment
repeats every 21 days for at least 4 courses in the absence of disease progression or
unacceptable toxicity.
In both parts of the study, patients who achieve a response may receive additional courses
of treatment.
After completion of study treatment, patients are followed periodically.
Inclusion Criteria
Inclusion
- Histologic proof of solid tumor malignancy
- ANC >= 1500/microliter
- PLT >= 150,000/microliter
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- AST =< 2.5 x ULN or AST =< 5 x ULN if liver involvement
- Serum creatinine =< 1.5
- Life expectancy >= 12 weeks
- ECOG performance status 0, 1, or 2
- Subjects with asymptomatic brain metastases are allowed
Exclusion
- ECOG PS 3 or 4
- Uncontrolled intercurrent illness including but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Patients must not have received chemotherapy or radiation therapy for at least four
weeks, and they must have recovered from any toxicities of previous treatment
(ongoing grade 1 dermatologic toxicities are allowable)
- Eligible patients should not be taking enzyme-inducing anticonvulsants due to the
potential of pharmacokinetic interactions
- Pregnant and nursing women
- Men or women of childbearing potential who are unwilling to employ adequate
contraception (condoms, diaphragm, birth control pills, injections, intrauterine
device [IUD] or abstinence, etc.)
- Other concurrent chemotherapy, immunotherapy, or radiotherapy
- HIV-positive patients receiving anti-retroviral therapy (HAART); there is a potential
for pharmacokinetic interactions
- Bisphosphonate therapy (e.g. pamidronate or zoledronate) will not be considered
investigational agents for the purpose of trial eligibility
- Pre-existing grade >= 2 neuropathy
- No previous treatment with PS-341 allowed, however there is no limit to other prior
therapy with chemotherapy, including topotecan, and radiation therapy
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Toxicity as assessed by NCI CTCAE v3.0
Outcome Time Frame:
21 days after the end of treatment
Safety Issue:
Yes
Principal Investigator
Robert Morgan
Investigator Role:
Principal Investigator
Investigator Affiliation:
Beckman Research Institute
Authority:
United States: Institutional Review Board
Study ID:
03109
NCT ID:
NCT00541359
Start Date:
January 2004
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- Neoplasms
Name | Location |
|---|---|
| City of Hope Medical Center | Duarte, California 91010 |
| City of Hope Medical Group Inc | Pasadena, California 91105 |
