Bortezomib and Topotecan Hydrochloride in Treating Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00541359
First received: October 5, 2007
Last updated: September 22, 2011
Last verified: September 2011

October 5, 2007
September 22, 2011
January 2004
June 2011   (final data collection date for primary outcome measure)
Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 21 days after the end of treatment ] [ Designated as safety issue: Yes ]
  • Overall survival
  • Progression-free survival
  • Time to progression
Complete list of historical versions of study NCT00541359 on ClinicalTrials.gov Archive Site
  • Overall survival [ Time Frame: 1 year from the end of treatment ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 1 year from the end of treatment ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: 1 year from the end of treatment ] [ Designated as safety issue: No ]
  • Levels of NF-kB activation [ Time Frame: At baseline and completion of treatment ] [ Designated as safety issue: No ]
Levels of NF-kB activation
Not Provided
Not Provided
 
Bortezomib and Topotecan Hydrochloride in Treating Patients With Advanced Solid Tumors
A Phase I Trial of PS-341 in Combination With Topotecan in Advanced Solid Tumor Malignancies

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with topotecan hydrochloride may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of topotecan hydrochloride when given together with bortezomib in treating patients with advanced solid tumors.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
  • Drug: bortezomib
    Given IV
    Other Names:
    • LDP 341
    • MLN341
    • PS-341
    • VELCADE
  • Drug: topotecan hydrochloride
    Given IV
    Other Names:
    • hycamptamine
    • Hycamtin
    • SKF S-104864-A
    • TOPO
  • Other: immunohistochemistry staining method
    Correlative studies
    Other Name: immunohistochemistry
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
Experimental: Arm I

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.

Interventions:
  • Drug: bortezomib
  • Drug: topotecan hydrochloride
  • Other: immunohistochemistry staining method
  • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
Not Provided
June 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00541359
03109, NCI-2009-01598, CDR0000570257
Yes
City of Hope Medical Center
City of Hope Medical Center
Not Provided
Principal Investigator: Robert Morgan Beckman Research Institute
City of Hope Medical Center
September 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP