Malignant Melanoma, Melanoma
Conditions
Keywords
stage III melanoma, stage IV melanoma, Depsipeptide
Brief 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.
Interventions
DRUGDepsipeptide
Given IV
Sponsors
National Cancer Institute (NCI)
ECOG-ACRIN Cancer Research Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Response to Depsipeptide | Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 3 years from study entry, up to 3 years | Response is evaluated using Solid Tumor Response Criteria (RECIST) and defined as either complete repose (CR) or partial response (PR). Per RECIST criteria, CR = disappearance of all target and nontarget lesions; PR = at least 30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. |
Participant flow
Recruitment details
The study was activated on January 11, 2005, accrued its first patient on October 4, 2005, and terminated on May 17, 2006 due to slow accrual. Four patients were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Depsipeptide Depsipeptide is administered as a 4-hour IV infusion weekly in doses of 13 mg/m\^2 for 3 weeks. Repeat cycle every 28 days until unacceptable toxicity or disease progression. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression | 4 |
Baseline characteristics
| Characteristic | Depsipeptide |
|---|---|
| Age, Continuous | 53.5 years |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 1 / 4 |
Outcome results
Primary
Proportion of Patients With Response to Depsipeptide
Response is evaluated using Solid Tumor Response Criteria (RECIST) and defined as either complete repose (CR) or partial response (PR). Per RECIST criteria, CR = disappearance of all target and nontarget lesions; PR = at least 30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.
Time frame: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 3 years from study entry, up to 3 years
Population: The study was terminated early due to slow accrual with final accrual of 4 patients. There are no plans to conduct a formal analysis for any outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Depsipeptide | Proportion of Patients With Response to Depsipeptide | NA percentage of participants |