Vorinostat and Bortezomib in Treating Patients With Metastatic or Unresectable Solid Tumors

NCT00227513 | Completed Phase 1

• 7 other identifiers: NCI-2009-00097CDR0000441195H-2005-0205CO 049066910P30CA014520U01CA062491
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of vorinostat and bortezomib in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)

  21 days

• Frequency and severity of toxicity incidents assessed by Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)

  Up to 5 years

Secondary Outcomes (4)

• Anti-tumor activity by tumor measurements assessed by RECIST

  Up to 5 years

• Peak plasma concentration (Cmax) of SAHA

  Days 1, 2, and 12

• Time to SAHA Cmax (Tmax)

  Days 1, 2, and 12

• Clearance of SAHA

  Days 1, 2, and 12

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral vorinostat (SAHA) twice daily on days 1-14 in step A. Patients receive oral vorinostat (SAHA) twice daily on days 1-4 and 8-11 in Step B and bortezomib IV over 3-5 seconds on days 2, 5, 9, and 12 during the first course and on days 1, 4, 8, and 11 during subsequent courses in both steps A and B. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 1-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 6 additional patients receive bortezomib at the MTD. Subsequent cohorts of 3-6 patients receive escalating doses of SAHA until the MTD of that drug is determined.

Drug: bortezomib; Drug: vorinostat

Interventions

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, VELCADE

Arm I

vorinostat DRUG

Given orally

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Arm I

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed malignancy, metastatic or unresectable disease
• Standard curative or palliative measures do not exist OR are no longer effective
• Measurable or evaluable disease
• No known brain metastases
• ECOG 0-2 OR Karnofsky 60-100%
• Life expectancy \> 12 weeks
• WBC ≥ 3,000/mm\^3
• Absolute neutrophil count ≥ 1,500/mm\^3
• Platelet count ≥ 100,000/mm\^3
• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• No history of myocardial infarction
• No symptomatic congestive heart failure
• No unstable angina pectoris

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

Bortezomib; Vorinostat

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• George Wilding

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 26, 2005
• First Posted: September 28, 2005
• Study Start: July 1, 2005
• Primary Completion: June 1, 2010
• Last Updated: February 24, 2014

Record last verified: 2013-04

Locations

US (1)