Vorinostat and Bortezomib in Treating Patients With Advanced Soft Tissue Sarcoma

NCT ID: NCT00937495

Last Updated: 2014-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2011-06-30

Brief Summary

This phase II trial is studying how well giving vorinostat together with bortezomib works in treating patients with advanced soft tissue sarcoma. Vorinostat and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with bortezomib may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the objective response rate in patients with advanced soft tissue sarcoma treated with vorinostat and bortezomib.

SECONDARY OBJECTIVES:

I. Characterize the toxicity of this regimen in these patients. II. Evaluate the progression-free survival and median overall survival of patients treated with this regimen.

OUTLINE:

Patients receive vorinostat orally (PO) once daily on days 1-14. Patients also receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 6 months for up to 2 years. (As of Addendum 7, patient follow-up no longer required.)

Conditions

Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (vorinostat, bortezomib)

Patients receive 400 mg vorinostat orally once daily on days 1-14. Patients also receive 1.3 mg/m\^2 bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

vorinostat

Intervention Type: DRUG

400 mg given PO

bortezomib

Intervention Type: DRUG

1.3 mg/m\^2 given IV

Interventions

vorinostat

400 mg given PO

Intervention Type: DRUG

bortezomib

1.3 mg/m\^2 given IV

Intervention Type: DRUG

Other Intervention Names

L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; LDP 341; MLN341; VELCADE

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed advanced, unresectable, or metastatic soft tissue sarcoma (STS)
• Measurable disease, defined as >= 1 lesion that can be accurately measured in >= 1 dimension as >= 2 cm by conventional techniques OR >= 1 cm by spiral computed tomography (CT) scan
• No small round cell tumors, including the following:

• Primitive neuroectodermal tumor
• Rhabdomyosarcoma
• Ewing sarcoma
• Osteosarcoma
• No known active and/or untreated brain metastases and/or brain metastases requiring ongoing therapy (e.g., corticosteroids)

• Treated, inactive brain metastases not requiring ongoing therapy allowed provided the brain metastases have been stable for >= 1 month as assessed by intracranial imaging AND there is no indication of increased vascularity of the treated metastases within 14 days before study entry as assessed by magnetic resonance imaging (MRI)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 OR Karnofsky PS 70-100%
• Life expectancy >= 12 weeks
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Total bilirubin normal
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance >= 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to take oral medication
• No peripheral neuropathy >= grade 2
• No concurrent uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia or myocardial infarction within the past 6 months
• Psychiatric illness and/or social situation that would limit compliance with study requirements
• No history of Torsades de Pointes
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to vorinostat or bortezomib
• No more than 1 prior systemic treatment for advanced STS, including investigational agents

• Adjuvant therapy is not considered a systemic regimen
• More than 2 weeks since prior valproic acid
• More than 4 weeks since prior and no concurrent chemotherapy (> 6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered

• Radiotherapy to bone metastasis within the past 2 weeks allowed provided there is active non-bone disease outside the radiation port
• No prior radiotherapy to >= 33% of the bone marrow
• No prior vorinostat or bortezomib
• No concurrent category I medications that are generally accepted to have a risk of causing Torsades de Pointes, including any of the following:

• Quinidine, procainamide, disopyramide
• Amiodarone, sotalol, ibutilide, dofetilide
• Erythromycin, clarithromycin
• Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
• No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients
• No other concurrent investigational agents for the primary malignancy
• No other concurrent anticancer therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Attia

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Florida

Jacksonville, Florida, United States

Johns Hopkins University

Baltimore, Maryland, United States

Mayo Clinic

Rochester, Minnesota, United States

Metro-Minnesota CCOP

Saint Louis Park, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

MC0778

Identifier Type: -

Identifier Source: secondary_id

CDR0000646715

Identifier Type: -

Identifier Source: secondary_id

MAYO-MC0778

Identifier Type: -

Identifier Source: secondary_id

N01CM62205

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-03810

Identifier Type: -

Identifier Source: org_study_id