Vorinostat and Bortezomib in Treating Patients With Advanced Soft Tissue Sarcoma

• ClinicalTrials.gov Identifier: NCT00937495
• Recruitment Status: Completed
• First Posted: July 13, 2009
• Results First Posted: November 21, 2013
• Last Update Posted: May 14, 2014
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma	Drug: vorinostat; Drug: bortezomib	Phase 2

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.)

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Suberoylanilide Hydroxamic Acid and Bortezomib in Advanced Soft Tissue Sarcomas
• Study Start Date: June 2009
• Actual Primary Completion Date: August 2010
• Actual Study Completion Date: June 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: vorinostat; 400 mg given PO; Other Names: L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; Drug: bortezomib; 1.3 mg/m^2 given IV; Other Names: LDP 341; MLN341; VELCADE

Outcome Measures

Primary Outcome Measures :

1. Confirmed Tumor Responses [ Time Frame: Up to 2 years ]

   The number of confirmed tumor responses is defined as a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) on two consecutive evaluations at least six weeks apart.

   Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest dimension (LD) of target lesions taking as reference the baseline sum LD.

Secondary Outcome Measures :

1. Progression Free Survival [ Time Frame: Up to 2 years ]
   Progression-free survival is defined as the time from registration to the time of progression or death, whichever comes first. The distribution and median of progression-free survival times will be estimated using the method of Kaplan-Meier.
2. Overall Survival [ Time Frame: Time from registration to death due to any cause, assessed up to 2 years ]
   The distribution of survival time will be estimated using the method of Kaplan-Meier.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Florida

Mayo Clinic in Florida

Jacksonville, Florida, United States, 32224-9980

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287-8936

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Metro-Minnesota CCOP

Saint Louis Park, Minnesota, United States, 55416

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, Wisconsin

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Steven Attia; Mayo Clinic

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00937495
• Other Study ID Numbers: NCI-2011-03810; MC0778; CDR0000646715; MAYO-MC0778; N01CM62205 ( U.S. NIH Grant/Contract )
• First Posted: July 13, 2009
• Results First Posted: November 21, 2013
• Last Update Posted: May 14, 2014
• Last Verified: September 2013

Additional relevant MeSH terms:

Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Bortezomib; Vorinostat; Antineoplastic Agents; Histone Deacetylase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action