Clinical trial NCT00022438: Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Metastatic Melanoma That Has Not Responded to Previous Treatment
Official title: Immunization of HLA-0201 Positive Patients With Metastatic Melanoma Using a Peptide From Tyrosinase-related Protein 2 (TRP-2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma (Skin)
Keywords: stage IV melanoma
recurrent melanoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Combining vaccine therapy with interleukin-2 may be an effective treatment for metastatic melanoma.

PURPOSE: Randomized phase II trial to compare the effectiveness of vaccine therapy plus interleukin-2 to that of vaccine therapy alone in treating patients who have metastatic melanoma that has not responded to previous treatment.

Detailed description: OBJECTIVES:

* Determine the clinical responses in patients with HLA-A0201-positive refractory metastatic melanoma treated with tyrosinase-related protein-2:180-188 peptide vaccine alone.
* Determine the clinical response rate of patients who have an immediate need to receive interleukin-2 (IL-2) in addition to this vaccine.
* Compare the immunologic response, in terms of changes in T-cell precursors before and after treatment, in patients treated with this vaccine with or without IL-2.
* Compare the toxicity profile of these regimens in these patients.

OUTLINE: This is a randomized, open-label study.

Patients who need immediate interleukin-2 (IL-2) receive tyrosinase-related protein-2 (TRP-2):180-188 peptide vaccine emulsified with Montanide ISA-51 on day 1 and high-dose IL-2 IV over 15 minutes once every 8 hours on days 2-5. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients who do not need immediate IL-2 are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive TRP-2:180-188 peptide vaccine emulsified with Montanide ISA-51 subcutaneously (SC) on day 1. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive TRP-2:180-188 peptide vaccine emulsified with Montanide ISA-51 SC once weekly on weeks 1-4. Treatment repeats every 7 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients who have a complete response (CR) receive 1 additional course after achieving CR. Patients who have progressive disease while receiving vaccine alone may cross over to receive peptide vaccine with IL-2 for at least 2 courses.

Patients are followed at 3 weeks.

PROJECTED ACCRUAL: A maximum of 83 patients (19-33 who need immediate interleukin-2 (IL-2); 15-25 per treatment arm who do not need immediate IL-2) will be accrued for this study within 1 year.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of metastatic melanoma

  * Refractory to standard therapy
  * No resectable locoregional disease
* HLA-A0201 positive
* Measurable disease
* Previously resected brain metastases, brain metastases stable after prior radiosurgery, or brain metastases less than 1 cm and without edema allowed

PATIENT CHARACTERISTICS:

Age:

* 16 and over

Performance status:

* ECOG 0-2

Life expectancy:

* More than 3 months

Hematopoietic:

* WBC at least 3,000/mm\^3
* Platelet count at least 90,000/mm\^3
* No coagulation disorders

Hepatic:

* Bilirubin no greater than 2.0 mg/dL (3.0 mg/dL for patients with Gilbert's syndrome)
* AST/ALT less than 3 times normal
* Hepatitis B surface antigen negative

Renal:

* Creatinine no greater than 2.0 mg/dL

Cardiovascular:

* No major medical illness of the cardiovascular system
* No cardiac ischemia\*
* No myocardial infarction\*
* No cardiac arrhythmias\* NOTE: \* For interleukin-2 (IL-2) administration

Pulmonary:

* No major medical illness of the respiratory system
* No obstructive or restrictive pulmonary disease (for IL-2 administration)

Immunologic:

* HIV negative
* No primary or secondary immunodeficiency
* No known immunodeficiency disease
* No autoimmune disease
* No active systemic infections

Other:

* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 3 weeks since prior biologic therapy for melanoma
* No prior immunization to tyrosinase-related protein-2 antigen
* No other concurrent biologic therapy for melanoma

Chemotherapy:

* At least 3 weeks since prior chemotherapy for melanoma and recovered
* No concurrent chemotherapy for melanoma

Endocrine therapy:

* At least 3 weeks since prior endocrine therapy for melanoma
* No concurrent systemic steroid therapy
* No concurrent endocrine therapy for melanoma

Radiotherapy:

* See Disease Characteristics
* At least 3 weeks since prior radiotherapy for melanoma and recovered
* No concurrent radiotherapy for melanoma

Surgery:

* See Disease Characteristics

Other:

* No other concurrent therapy for melanoma

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
Study officials:
affiliation: NCI - Surgery Branch
name: Steven A. Rosenberg, MD, PhD
role: STUDY_CHAIR
References: