Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	PMH-PHL-040 NCI-6916, 6916, NCT00121225

Objectives

Primary

1. Determine the objective response rate in patients with metastatic or unresectable melanoma treated with vorinostat.

Secondary

1. Determine time to progression in patients treated with this drug.
2. Determine the utility of HP1 and/or macro H2A nuclear foci as biomarkers of response in patients treated with this drug.
3. Correlate the presence of 72R or 72P variant p53 polymorphisms with response and time to progression in patients treated with this drug.
4. 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.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed melanoma
  • Metastatic or unresectable disease
• The following melanoma types are allowed:
  • Cutaneous
  • Mucosal
  • Ocular
  • Unknown primary
• Evidence of residual, recurrent, or metastatic disease by radiographic examination
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
  • Tumor lesions located within a previously irradiated volume that are the only site of measurable disease must have clear evidence of progression
• No known brain metastases

Prior/Concurrent Therapy:

Biologic therapy

• Prior adjuvant interferon for stage II or stage III disease allowed
• Prior vaccine therapy as adjuvant therapy or for metastatic disease allowed
• No more than 1 prior cytokine and/or chemotherapy regimen for metastatic disease
• No concurrent prophylactic hematopoietic colony-stimulating factors except erythropoietin

Chemotherapy

• See Biologic therapy
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• No concurrent steroids except topical or inhaled steroids

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• At least 2 weeks since prior valproic acid
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• At least 3 months

Hematopoietic

• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal

Renal

• Creatinine normal

  OR

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to suberoylanilide hydroxamic acid
• No other uncontrolled illness

Expected Enrollment

A total of 32 patients will be accrued for this study within 10-16 months.

Outcomes

Objective response rate using measurable disease as measured by RECIST criteria

Time to progression
Progression-free survival at 2 months
Effect of vorinostat on HP1 and macro H2A nuclear foci
Effect of vorinostat on vascular endothelial growth factor and basic fibroblast growth factor
Correlation of WT, 72R, and 72P p53 alleles with response

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.

Trial Contact Information

Trial Lead Organizations

Princess Margaret Hospital

Naomi Balzer-Haas, MD, Principal investigator		Ph: 215-615-5121 Email: naomi.haas@uphs.upenn.edu

Registry Information
Official Title		A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Advanced Melanoma
Trial Start Date		2005-09-05
Trial Completion Date		2006-07-22 (estimated)
Registered in ClinicalTrials.gov		NCT00121225
Date Submitted to PDQ		2005-06-08
Information Last Verified		2008-12-02
NCI Grant/Contract Number		CM62203

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