Clinical trial NCT00109863: Hu14.18-Interleukin-2 Fusion Protein in Treating Patients With Advanced Melanoma
Official title: Phase II Trial of Hu14.18-IL2 (EMD 273063) in Subjects With Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma (Skin)
Keywords: recurrent melanoma
stage IV melanoma
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-05-04
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Objective response rate and duration of response by clinical exam and radiology studies after every 2 courses
Secondary outcomes:
measure: Adverse events by clinical assessment daily during treatment and weekly after completion of study treatment
measure: Immunologic activation induced by hu14.18-interleukin-2 after every 2 courses
measure: Induction of anti-idiotypic antibodies on days 1, 3, 4, and 8 of each course
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Mark R. Albertini, MD
role: STUDY_CHAIR
References: