Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma

Condition(s) targeted: Intraocular Melanoma; Melanoma (Skin)

Intervention: vorinostat (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Princess Margaret Hospital, Canada

Official(s) and/or principal investigator(s):
Naomi S. Balzer-Haas, MD, Principal Investigator, Affiliation: University of Pennsylvania

RATIONALE: 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.

PURPOSE: This phase II trial is studying how well vorinostat works in treating patients with metastatic or unresectable melanoma.

Official title: A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Advanced Melanoma

Study design: Treatment, Open Label

Primary outcome: Objective response rate using measurable disease as measured by RECIST criteria

Secondary outcome:

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

Detailed description: OBJECTIVES:

Primary

- Determine the objective response rate in patients with metastatic or unresectable

melanoma treated with vorinostat.

Secondary

- Determine time to progression in patients treated with this drug.

- Determine the utility of HP1 and/or macro H2A nuclear foci as biomarkers of response in

patients treated with this drug.

- Correlate the presence of 72R or 72P variant p53 polymorphisms with response and time to

progression in patients treated with this drug.

- 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.

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

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/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

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

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

Margaret and Charles Juravinski Cancer Centre, Hamilton, Ontario L8V 5C2, Canada; Recruiting
Sebastien Hotte, MD, Phone: 905-387-9495, ext. 64784, Email: sebastien.hotte@hrcc.on.ca

Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada; Recruiting
Ian C. Quirt, MD, Phone: 416-946-4501 ext. 2249, Email: ian.quirt@uhn.on.ca

Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104-4283, United States; Recruiting
Clinical Trials Office - Abramson Cancer Center of the Univers, Phone: 800-474-9892

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: September 2005
Last updated: October 22, 2008