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Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma

Primary Purpose

Ciliary Body and Choroid Melanoma, Medium/Large Size, Extraocular Extension Melanoma, Iris Melanoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
vorinostat
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ciliary Body and Choroid Melanoma, Medium/Large Size

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologically/cytologically confirmed melanoma that is metastatic/unresectable Residual, recurrent, or metastatic disease by radiographic examination. Measurable disease (at least 1 lesion in at least 1 dimension (longest diameter) as >20mm with conventional techniques or >10mm with spiral CT scan, within 4 weeks prior to registration No prior therapy or 1 prior treatment (cytokine/chemotherapy/combination) for metastatic disease allowed. Patients should not take valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment. At least 4 weeks from prior therapy to be eligible or 6 weeks if last regimen included BCNU or mitomycin C Age>=18 years Life expectancy >=3 months. ECOG<2 (Karnofsky ≥60%) Leukocytes >3,000/mcL Absolute neutrophil count >1,500/mcL Platelets >100,000/mcL Total bilirubin within institutional limits AST/ALT≤2.5Xinstitutional ULN Creatinine within institutional limits OR creatinine clearance >60mL/min/1.73 m2 if creatinine levels above institutional limits Eligibility of patients taking medications with potential to affect activity/PK of Vorinostat will be determined by PI Must not use concomitant steroids except topical/inhaled use Vorinostat effects on developing human fetus are unknown. Women of childbearing potential (WOCBP) and sexually active males must agree to use accepted/effective contraception method prior to study entry and for duration of the study Ability to understand/willingness to sign written informed consent Must have paraffin block of tumor tissue available for future studies Exclusion Criteria: Chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study May not be receiving any other investigational agents Known brain metastases History of allergic reactions attributed to compounds of similar chemical/biologic composition to Vorinostat Uncontrolled intercurrent illness including but not limited to ongoing/active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women excluded because Vorinostat is a HDAC inhibitor agent with potential for teratogenic or abortifacient effects HIV-positive patients receiving combination antiretroviral therapy are ineligible because of potential for PK interactions with Vorinostat

Sites / Locations

  • Fox Chase Cancer Center
  • Fox Chase Cancer Center
  • Juravinski Cancer Centre at Hamilton Health Sciences
  • Princess Margaret Hospital Phase 2 Consortium
  • University Health Network-Princess Margaret Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter.

Outcomes

Primary Outcome Measures

Objective Response Rate Assessed by Response Evaluation Criteria for Solid Tumors (RECIST)
Per Response Evaluation Criteria in Solid Tumours Criteria (RECIST v1.0) for target lesions and are assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in sum of longest diameter of target lesions; Objective Response (OR) = CR+ PR.

Secondary Outcome Measures

Time to Progression Assessed by RECIST
Difference in HP1 and MacroH2A Nuclear Foci Expression Between Progressive Minus Stable Disease Outcomes
Macro H2A and HP1 expression levels were compared through analysis of log fold changes in antibody expression in a multivariate general linear model between progressive disease and stable disease outcomes.
Number of Patients With p53 Allelic Variations (72R or 72P)
Participants were assessed for p53 allelic variation at baseline
Comparison of VEGF Serum Levels to Response to Vorinostat
Blood specimens were collected from participants on Day 1 Cycle 1 prior to treatment (baseline), Day 1 3-4 hours following Vorinostat ingestion, Day 8 and Day 15. VEGF serum concentrations were detected using the Luminex multiplexed assay, where the median fluorescence intensity results were analyzed by a weighted five-parameter logistic method. The values were averaged across all time points per participant.

Full Information

First Posted
July 19, 2005
Last Updated
January 9, 2019
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00121225
Brief Title
Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma
Official Title
A Phase II Study of Vorinostat in Patients With Advanced Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial is studying how well vorinostat works in treating patients with metastatic or unresectable melanoma. Vorinostat 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.
Detailed Description
PRIMARY OBJECTIVE: I. Determine the objective response rate in patients with metastatic or unresectable melanoma treated with vorinostat. SECONDARY OBJECTIVES: I. Determine time to progression in patients treated with this drug. II. Determine the utility of HP1 and/or macro H2A nuclear foci as biomarkers of response in patients treated with this drug. III. Correlate the presence of 72R or 72P variant p53 polymorphisms with response and time to progression in patients treated with this drug. IV. Determine gene expression profiles that may predict response to this drug and gene expression changes that occur after treatment with this drug in these patients. OUTLINE: This is a multicenter study. Patients receive oral vorinostat once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for 4 weeks and then every 3 months thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ciliary Body and Choroid Melanoma, Medium/Large Size, Extraocular Extension Melanoma, Iris Melanoma, Uveal Melanoma, Recurrent Intraocular Melanoma, Recurrent Melanoma, Stage IV Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter.
Intervention Type
Drug
Intervention Name(s)
vorinostat
Other Intervention Name(s)
L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Intervention Description
Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter.
Primary Outcome Measure Information:
Title
Objective Response Rate Assessed by Response Evaluation Criteria for Solid Tumors (RECIST)
Description
Per Response Evaluation Criteria in Solid Tumours Criteria (RECIST v1.0) for target lesions and are assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in sum of longest diameter of target lesions; Objective Response (OR) = CR+ PR.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Time to Progression Assessed by RECIST
Time Frame
Up to 5 years
Title
Difference in HP1 and MacroH2A Nuclear Foci Expression Between Progressive Minus Stable Disease Outcomes
Description
Macro H2A and HP1 expression levels were compared through analysis of log fold changes in antibody expression in a multivariate general linear model between progressive disease and stable disease outcomes.
Time Frame
Baseline and day 15
Title
Number of Patients With p53 Allelic Variations (72R or 72P)
Description
Participants were assessed for p53 allelic variation at baseline
Time Frame
Baseline
Title
Comparison of VEGF Serum Levels to Response to Vorinostat
Description
Blood specimens were collected from participants on Day 1 Cycle 1 prior to treatment (baseline), Day 1 3-4 hours following Vorinostat ingestion, Day 8 and Day 15. VEGF serum concentrations were detected using the Luminex multiplexed assay, where the median fluorescence intensity results were analyzed by a weighted five-parameter logistic method. The values were averaged across all time points per participant.
Time Frame
Baseline, Day 1, Day 8 and Day 15

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically/cytologically confirmed melanoma that is metastatic/unresectable Residual, recurrent, or metastatic disease by radiographic examination. Measurable disease (at least 1 lesion in at least 1 dimension (longest diameter) as >20mm with conventional techniques or >10mm with spiral CT scan, within 4 weeks prior to registration No prior therapy or 1 prior treatment (cytokine/chemotherapy/combination) for metastatic disease allowed. Patients should not take valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment. At least 4 weeks from prior therapy to be eligible or 6 weeks if last regimen included BCNU or mitomycin C Age>=18 years Life expectancy >=3 months. ECOG<2 (Karnofsky ≥60%) Leukocytes >3,000/mcL Absolute neutrophil count >1,500/mcL Platelets >100,000/mcL Total bilirubin within institutional limits AST/ALT≤2.5Xinstitutional ULN Creatinine within institutional limits OR creatinine clearance >60mL/min/1.73 m2 if creatinine levels above institutional limits Eligibility of patients taking medications with potential to affect activity/PK of Vorinostat will be determined by PI Must not use concomitant steroids except topical/inhaled use Vorinostat effects on developing human fetus are unknown. Women of childbearing potential (WOCBP) and sexually active males must agree to use accepted/effective contraception method prior to study entry and for duration of the study Ability to understand/willingness to sign written informed consent Must have paraffin block of tumor tissue available for future studies Exclusion Criteria: Chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study May not be receiving any other investigational agents Known brain metastases History of allergic reactions attributed to compounds of similar chemical/biologic composition to Vorinostat Uncontrolled intercurrent illness including but not limited to ongoing/active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women excluded because Vorinostat is a HDAC inhibitor agent with potential for teratogenic or abortifacient effects HIV-positive patients receiving combination antiretroviral therapy are ineligible because of potential for PK interactions with Vorinostat
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naomi Balzer-Haas
Organizational Affiliation
Princess Margaret Hospital Phase 2 Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111-2497
Country
United States
Facility Name
Fox Chase Cancer Center
City
Rockledge
State/Province
Pennsylvania
ZIP/Postal Code
19046
Country
United States
Facility Name
Juravinski Cancer Centre at Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Princess Margaret Hospital Phase 2 Consortium
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
University Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
24464266
Citation
Haas NB, Quirt I, Hotte S, McWhirter E, Polintan R, Litwin S, Adams PD, McBryan T, Wang L, Martin LP, vonMehren M, Alpaugh RK, Zweibel J, Oza A. Phase II trial of vorinostat in advanced melanoma. Invest New Drugs. 2014 Jun;32(3):526-34. doi: 10.1007/s10637-014-0066-9. Epub 2014 Jan 25.
Results Reference
result

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Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma

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