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

Phase 2

Terminated

• Conditions: Malignant Melanoma; Melanoma
• Interventions: Drug: Depsipeptide

• Registration Number: NCT00104884
• Lead Sponsor: ECOG-ACRIN Cancer Research Group

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.

Study Timeline

• Study First Submitted: 2005-03-03
• Study First Submitted QC: 2005-03-03
• Study First Posted: 2005-03-04
• Study Start: 2005-10-04
• Primary Completion: 2006-05
• Study Completion: 2009-03
• Results First Submitted: 2015-12-15
• Results First Submitted QC: 2016-02-01
• Results First Posted: 2016-03-02
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-13
• Last Update Posted: 2023-06-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Depsipeptide	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.

Primary Outcome Measures

Name	Time	Method
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.