Bortezomib and Topotecan Hydrochloride in Treating Patients With Advanced Solid Tumors

NCT00541359 | Completed Phase 1 DMC

• 3 other identifiers: 03109NCI-2009-01598CDR0000570257
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• Toxicity as assessed by NCI CTCAE v3.0

  21 days after the end of treatment

Secondary Outcomes (4)

• Overall survival

  1 year from the end of treatment

• Progression-free survival

  1 year from the end of treatment

• Time to progression

  1 year from the end of treatment

• Levels of NF-kB activation

  At baseline and completion of treatment

Study Arms (1)

Arm I

EXPERIMENTAL

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; Drug: topotecan hydrochloride; Other: immunohistochemistry staining method; Other: pharmacological study

Interventions

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, PS-341, VELCADE

Arm I

topotecan hydrochloride DRUG

Given IV

Also known as: hycamptamine, Hycamtin, SKF S-104864-A, TOPO

Arm I

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope Medical Group Inc

Pasadena, California, 91105, United States

Location

MeSH Terms

Interventions

Bortezomib; Topotecan; trioctyl phosphine oxide; Immunohistochemistry

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques

Study Officials

• Mihaela Cristea, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2007
• First Posted: October 10, 2007
• Study Start: January 1, 2004
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: August 9, 2017

Record last verified: 2017-08

Locations

US (2)