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

University of Wisconsin (UW)

Status and phase: Completed; Phase 2

Conditions: Melanoma (Skin)

Treatments: Biological: hu14.18-IL2 fusion protein

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00109863

NCI-6304

A533300 (Other Identifier)

CO04601 (Other Identifier)

R01CA032685 (U.S. NIH Grant/Contract)

H-2004-0396 (Other Identifier)

NCI-2009-00051 (Registry Identifier)

P30CA014520 (U.S. NIH Grant/Contract)

CDR0000426431

SMPH\HUMAN ONCOLOGY\HUMAN ONCO (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 14 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 1 patient group

Hu14.18-IL2 Treatment

Experimental group

Description:

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.

Treatment:

Biological: hu14.18-IL2 fusion protein