This pilot study will assess the safety and efficacy of Pivanex alone in patients with
malignant melanoma who have relapsed after treatment with chemotherapy or Interleukin-2
(IL-2). Pivanex is an investigational agent.
Rationale: Pivanex is a histone deacetylase inhibitor that induces tumor differentiation,
inhibits proliferation, and induces apoptosis. Pivanex has been generally well tolerated in
clinical trials and has shown preliminary evidence of efficacy in patients with non-small
cell lung cancer. Pivanex has shown in-vitro and in-vivo evidence of anti-tumor activity
against melanoma and, therefore, represents a promising therapeutic approach to patients
with malignant melanoma.
Purpose: This open-label trial will determine the response rate of Pivanex in patients with
- Determine time to disease progression
- Determine overall survival
- Determine the safety profile of Pivanex in malignant melanoma
Outline: This is an open-label, single center study in patients with malignant melanoma
whose disease has progressed or failed to respond to chemotherapy or Interleukin-2 (IL-2).
Patients will be treated with 2.5 g/m2 of Pivanex administered intravenously over 6 hours
daily on Days 1 – 3.
Treatment will be repeated every 21 days until tumor progression or the patient is withdrawn
from treatment for other protocol-specified reasons. Tumor status will be assessed prior to
every odd-numbered treatment cycle using the Response Evaluation Criteria in Solid Tumors
(RECIST) method. Patients who continue to experience tumor response or stabilization at the
time treatment is discontinued will be followed every 12 weeks for tumor status until
- Histologically or cytologically confirmed melanoma, previously treated with
chemotherapy or IL-2
- Recurrent or progressive disease after treatment.
- Measurable disease.
- Males and females, age ≥ 18 years.
- Adequate renal function with creatinine ≥ 1.5 mg/dl.
- Adequate liver function with alkaline phosphatase <= 2.5 X upper limit of normal,
SGOT and SGPT <= 1.5 X upper limit of normal and total bilirubin <= 1.5 X upper limit
- Adequate bone marrow function: platelets ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL, and
absolute neutrophil count (ANC)≥ 1,500 cells/mm3.
- Able to give informed consent.
- Must have discontinued previous surgery, radiation therapy or cancer chemotherapy at
least four weeks prior to randomization (six weeks if a prior nitrosourea or
mitomycin C), with recovery from treatment-associated toxicity. Localized palliative
radiation therapy to non-target lesions is permitted within the four weeks prior to
- A predicted life expectancy of at least 6 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Receipt of more than three (3) systemic treatment regimens for malignant melanoma
- A second malignancy within the last 5 years other than curatively treated
carcinoma-in-situ or non-melanoma skin cancer.
- Pregnant or lactating females. Females of childbearing potential must have a negative
pregnancy test and all male and female patients of reproductive potential must agree
to use adequate birth control.
- Known HIV-positive patients.
- Acute medical problems, such as ischemic heart or lung disease or uncontrolled
- Patients with any underlying medical conditions or circumstance, which would
contraindicate therapy with study treatment, affect compliance or impair evaluation
of study endpoints.
- Patients receiving investigational agents within 4 weeks of randomization.
- Known allergy to reagents in the study.
- Symptomatic or untreated brain metastases – Patients with brain metastases are
eligible if they are clinically and neurologically stable for ≥ 4 weeks since therapy
(radiation therapy, radiosurgery/gamma knife, surgical resection) as determined by
the investigator and either off corticosteroids or on a stable dose of