Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: FR901228 in Treating Patients With Unresectable Stage III or Stage IV Malignant Melanoma

Summary: RATIONALE: Drugs used in chemotherapy, such as FR901228, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
  PURPOSE: This phase II trial is studying how well FR901228 works in treating patients with unresectable stage III or stage IV malignant melanoma.

Detailed description: OBJECTIVES:
  Primary
  -  Determine the response rate in patients with unresectable stage III or stage IV malignant melanoma treated with FR901228 (depsipeptide).
  Secondary
  -  Determine the progression-free and overall survival of patients treated with this drug.
  -  Determine the toxicity profile of this drug in these patients.
  OUTLINE: This is a multicenter study.
  Patients receive FR901228 (depsipeptide) intravenously (IV) over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.
  PROJECTED ACCRUAL: A total of 22-40 patients will be accrued for this study within 18 months.

Eligibility: Inclusion Criteria:
  -  Stage III unresectable or American Joint Committee on Cancer (AJCC) stage IV cutaneous, mucosal, ocular, or unknown primary melanoma with measurable disease by physical examination or imaging studies.
  -  Palpable cutaneous or nodal metastases suitable for punch, trucut, or similar biopsy if the patient agrees.
  -  Normal electrocardiogram (EKG)
  -  Left ventricular ejection fraction (LVEF) > 40% by Multi Gated Acquisition Scan (MUGA)
  -  Corrected QT (QTc) < 500 msec
  -  Age greater than or equal to 18
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception
  -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
  -  Normal organ and marrow function
  -  Patients on hydrochorthiazide should be switched to a potassium-sparing diuretic or another antihypertensive
  -  At least 4 weeks since prior radiotherapy
  -  Patients with cardiac hypertrophy may be enrolled but should be carefully monitored.
  Exclusion Criteria:
  -  Prior FR901228 (depsipeptide)
  -  Prior chemotherapy
  -  Other concurrent chemotherapy
  -  Active central nervous system (CNS) metastases by brain computed tomography (CT) scan or magnetic resonance imaging (MRI)
  -  History of coronary atherosclerotic heart disease
  -  History of myocardial infarction
  -  History of congestive heart failure
  -  Non-melanoma malignancy within the past 5 years except carcinoma in situ or squamous cell or basal cell skin cancer
  -  Pregnant or nursing women
  -  Conditions that in the opinion of the investigator would interfere with the ability of the patient to complete this protocol
  -  History of allergic reactions attributed to compounds of similar chemical or biologic composition to Depsipeptide
  -  Co-medication with an agent that causes QTc prolongation
  -  Human immunodeficiency virus (HIV) positive patients receiving combination anti-retroviral therapy
  -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
  -  Concurrent radiotherapy
  -  Left ventricular hypertrophy (LVH) on their baseline EKG tracing

Relevance to patient case: not relevant