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
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: bortezomib
Drug: topotecan hydrochloride
Other: immunohistochemistry staining method
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of PS-341 in Combination With Topotecan in Advanced Solid Tumor Malignancies

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 21 days after the end of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 40
Study Start Date: January 2004
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00541359

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
City of Hope Medical Group Inc
Pasadena, California, United States, 91105
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Robert Morgan Beckman Research Institute
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00541359     History of Changes
Other Study ID Numbers: 03109, NCI-2009-01598, CDR0000570257
Study First Received: October 5, 2007
Last Updated: September 22, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasms
Bortezomib
Topotecan
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014