Hu14.18-Interleukin-2 Fusion Protein in Treating Patients With Advanced Melanoma

Study Overview
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Brief Summary
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RATIONALE: Biological therapies, such as hu14.18-interleukin-2 fusion protein, may stimulate the immune system in different ways and stop tumor cells from growing. PURPOSE: This phase II trial is studying how well hu14.18-interleukin-2 fusion protein works in treating patients with advanced melanoma.

Detailed Description
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OBJECTIVES: Primary Determine the clinical antitumor activity of hu14.18-interleukin-2 fusion protein in patients with advanced melanoma. Determine the duration of response in patients treated with this drug. Secondary Determine the adverse events in patients treated with this drug. Determine the in vivo immunologic activation in patients treated with this drug. Determine the induction of anti-hu14.18 and anti-interleukin-2 antibodies in patients treated with this drug. Determine tumor antigen recognition by this drug in select patients with cutaneous metastatic tumors, as measured by binding of the drug to the cutaneous metastatic tumor and microscopic changes (including immune cell density and phenotype) of the tumor tissue. OUTLINE: Patients receive hu14.18-interleukin-2 fusion protein IV over 4 hours on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of symptomatic disease progression or unacceptable toxicity. Patients then undergo disease reassessment. Patients with an objective partial or complete clinical response or stable disease receive 2 additional courses of treatment. PROJECTED ACCRUAL: A total of 14-30 patients will be accrued for this study within 7-15 months.

Official Title
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Phase II Trial of Hu14.18-IL2 (EMD 273063) in Subjects With Advanced Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: hu14.18-IL2 fusion protein


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant melanoma Advanced disease Measurable disease by clinical assessment or imaging No known standard curative therapy exists Disease no longer controlled by surgery, chemotherapy, or radiotherapy No clinically detectable pleural effusion or ascites No brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic WBC ≥ 3,500/mm^3 OR Granulocyte count ≥ 2,000/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10.0 g/dL Hepatic AST and ALT < 2 times normal Bilirubin < 2.0 mg/dL Hepatitis B surface antigen negative No clinical evidence of hepatitis Renal Creatinine < 2.0 mg/dL OR Creatinine clearance ≥ 60 mL/min Cardiovascular No ischemic cardiac disease, congestive heart failure, or myocardial infarction within the past 6 months No uncontrolled cardiac rhythm disturbance No myocardial ischemia or heart failure by exercise radionuclide scan for patients with a history of cardiac disease, significant risk factors for coronary artery disease, or ≥ 65 years of age Pulmonary Pulmonary function normal by exercise radionuclide scan for patients with a history of cardiac disease, significant risk factors for coronary artery disease, or ≥ 65 years of age Immunologic HIV negative No known hypersensitivity to the study drug, Tween-80®, or human immunoglobulin No uncontrolled active infection Neurologic No seizure disorder No objective peripheral neuropathy ≥ grade 2 No clinically significant neurologic deficit Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Must consent to the placement of a central venous line OR demonstrate stable peripheral IV access Must be willing and able to discontinue antihypertensive medications (if advised to do so) on the days of study drug infusion No uncontrolled active peptic ulcer No known grade 4 side effects related to prior interleukin-2 No diabetes mellitus that has required systemic therapy (e.g., oral hypoglycemic agents or insulin) within the past 3 months No other significant illness No significant psychiatric disability PRIOR CONCURRENT THERAPY: Biologic therapy Prior monoclonal antibodies for biologic therapy, tumor imaging, purging of autologous bone marrow/stem cells for re-infusion, or for any other reason allowed provided there is documented absence of detectable antibody to hu14.18 by serology No concurrent growth factors Chemotherapy No immediate requirement for palliative chemotherapy No concurrent anticancer chemotherapy Endocrine therapy More than 2 weeks since prior and no concurrent corticosteroids (e.g., dexamethasone) No immediate requirement for palliative hormonal therapy Radiotherapy No immediate requirement for palliative radiotherapy Concurrent palliative radiotherapy to localized painful lesions allowed provided ≥ 1 measurable or evaluable lesion is not irradiated AND the irradiated lesion is not used to assess tumor response Surgery More than 3 weeks since prior major surgery No prior organ allografts Other More than 2 weeks since other prior and no concurrent immunosuppressive drugs No prior standard or experimental systemic therapy for stage IV melanoma No concurrent myelosuppressive antineoplastic drugs

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hu14.18-IL2 Treatment<br>Hu14.18-IL2 will be given on days 1, 2, and 3 of each course of therapy as a 4 hour continuous IV infusion at a daily dose of 6 mg/m2. Treatment courses will be repeated every 28 days at the same dose. | Biological: hu14.18-IL2 fusion protein<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate and duration of response by clinical exam and radiology studies after every 2 courses |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events by clinical assessment daily during treatment and weekly after completion of study treatment |  |  | 
| Immunologic activation induced by hu14.18-interleukin-2 after every 2 courses |  |  | 
| Induction of anti-idiotypic antibodies on days 1, 3, 4, and 8 of each course |  |  | 

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