Know Cancer

or
forgot password

A Phase I Trial of PS-341 in Combination With Topotecan in Advanced Solid Tumor Malignancies


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

Thank you

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 CenterDuarte, California  91010
City of Hope Medical Group IncPasadena, California  91105