Bortezomib and Topotecan in Treating Patients With Advanced Solid Tumors - Full Text View

Sponsors and Collaborators:	Beckman Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00541359

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, 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 may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of topotecan 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 Procedure: high performance liquid chromatography Procedure: immunohistochemistry staining method	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Topotecan hydrochloride Topotecan Bortezomib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Trial of PS-341 in Combination With Topotecan in Advanced Solid Tumor Malignancies

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Time to progression [ Designated as safety issue: No ]

Secondary Outcome Measures:

Levels of NF-kB activation [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	January 2004
Estimated Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To assess the safety and feasibility of combining bortezomib with topotecan hydrochloride in patients with advanced solid tumor malignancies.
To define the maximum tolerated dose (MTD) of topotecan hydrochloride when administered in combination with a fixed dose of bortezomib.
To describe the toxicities at each dose studied.
To evaluate the pharmacokinetics of topotecan hydrochloride when given in combination with bortezomib at the MTD.

Secondary

To perform correlative studies on patient tissue to investigate 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.

Some patients undergo tumor tissue and blood sample collection periodically for correlative and pharmacokinetic studies. Samples are analyzed for NF-kB activation via immunohistochemical analysis and total topotecan and closed lactone ring form of topotecan via high performance liquid chromatography.

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

DISEASE CHARACTERISTICS:

Histologically confirmed solid tumor
Asymptomatic brain metastases allowed

PATIENT CHARACTERISTICS:

Inclusion criteria:

ECOG performance status 0-2
Life expectancy ≥ 12 weeks
Absolute neutrophil count ≥ 1,500/μL
Platelet count ≥ 150,000/μL
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST ≤ 2.5 times ULN ( ≤ 5 times ULN if liver involvement)
Serum creatinine ≤ 1.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

Exclusion criteria:

ECOG performance status 3 or 4
Uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
Psychiatric illness/social situations that would limit compliance with study requirements
Preexisting neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

At least 4 weeks since prior chemotherapy or radiotherapy and recovered
No prior bortezomib
- There is no limit to other prior chemotherapy, radiotherapy, or topotecan hydrochloride
No concurrent antiretroviral therapy for HIV-positive patients
No other concurrent chemotherapy, immunotherapy, or radiotherapy
No concurrent enzyme-inducing anticonvulsants
Bisphosphonate therapies (e.g., pamidronate or zoledronate) will not be considered investigational agents for this trial

Contacts and Locations

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

Locations

United States, California
City of Hope Comprehensive Cancer Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org
City of Hope Medical Group	Recruiting
Pasadena, California, United States, 91105
Contact: Contact Person 800-826-4673 becomingapatient@coh.org

Sponsors and Collaborators

Beckman Research Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Robert J. Morgan, MD

Beckman Research Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000570257, CHNMC-03109
Study First Received:	October 5, 2007
Last Updated:	December 9, 2008
ClinicalTrials.gov Identifier:	NCT00541359
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Study placed in the following topic categories:

Bortezomib
Topotecan

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on January 14, 2009