Sulindac and Epirubicin in Treating Patients With Metastatic Malignant Melanoma

Study Overview
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Brief Summary
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RATIONALE: Sulindac may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as epirubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sulindac together with epirubicin may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving sulindac together with epirubicin works in treating patients with metastatic malignant melanoma.

Detailed Description
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OBJECTIVES: Primary To estimate the non-comparative efficacy of sulindac and epirubicin hydrochloride in patients with metastatic malignant melanoma. Secondary To characterize the toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive oral sulindac 2 hours prior to receiving epirubicin hydrochloride IV over 15 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Previously collected tumor blocks are assessed for cancer resistance markers by IHC. After completion of study treatment, patients are followed for 1 month, and then every 3 months thereafter.

Official Title
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Phase II Trial of the Multi-Drug Resistance Protein Modulating Agent Sulindac in Combination With Epirubicin in Patients With Advanced Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Drug: epirubicin hydrochloride
* Drug: sulindac
* Other: immunologic technique


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant melanoma Metastatic disease Tumor block available for resistance marker analysis Measurable or evaluable disease No active brain metastases except for patients who have undergone successful complete excision of solitary brain metastasis PATIENT CHARACTERISTICS: Karnofsky performance status 80-100% ANC > 1 x 10^9/L Platelet count > 100 x 10^9/L Hemoglobin > 9 g/dL Serum bilirubin normal (except in patients with benign congenital hyperbilirubinemia) Not pregnant or nursing Negative pregnancy test Normal cardiac ejection fraction, cardiac wall motion, and ECG No active heart disease, including any of the following: Myocardial infarction within the past year Pericarditis Existing hypertension requiring treatment No other active serious medical or psychiatric disease No prior or concurrent malignancy, other than basal cell carcinoma of the skin , or carcinoma in-situ of the cervix PRIOR CONCURRENT THERAPY: No prior anthracycline or anthracenedione-containing chemotherapy regimen No prior cardiac radiotherapy No major surgery within the past 2 weeks No participation in any clinical trial within the past 4 weeks No other concurrent anticancer therapies Concurrent bisphosphonates allowed in patients with bony metastases with extra-osseous measurable or evaluable lesions No other concurrent experimental medications

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epirubicin hydrochloride (75mg/m2 i.v.) Sulindac: 600mg<br> | Drug: epirubicin hydrochloride<br> <br> Drug: sulindac<br> <br> Other: immunologic technique<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To estimate the non-comparative efficacy of this treatment combination in patients with malignant melanoma. Response will be assessed using the RECIST Criteria | The interim analysis will study the objective response to treatment in the first cohort of 29 patients. Response will be assessed according to NCI -Response Evaluation Criteria in Solid Tumors (RECIST) guidelines | Ongoing throughout trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity according to NCI CTCAE v.3.0 |  | Ongoing throughout trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV melanoma