Clinical trial NCT00019682: Aldesleukin With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Melanoma
Official title: A Phase III Multi-Institutional Randomized Study of Immunization With the gp100: 209-217 (210M) Peptide Followed by High Dose IL-2 vs. High Dose IL-2 Alone in Patients With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Recurrent Melanoma
Stage IIIA Skin Melanoma
Stage IIIB Skin Melanoma
Stage IIIC Skin Melanoma
Stage IV Skin Melanoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 185
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase III trial studies aldesleukin with vaccine therapy to see how well it works compared to aldesleukin alone in treating patients with melanoma that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Aldesleukin may stimulate a person's white blood cells to kill melanoma cells. Vaccines may make the body build an immune response to kill tumor cells. It is not yet known whether combining aldesleukin with vaccine therapy is more effective than aldesleukin alone in treating melanoma.

Detailed description: PRIMARY OBJECTIVES:

I. To identify whether the addition of the peptide vaccine to high dose interleukin (IL)-2 (aldesleukin) can result in a clinical response rate which may be superior to that found in similar patients treated with high dose IL-2 alone.

SECONDARY OBJECTIVES:

I. To evaluate the toxicity profile of patients treated on this trial, according to the regimen received.

II. To compare the disease free/progression free survival of patients treated on both arms of the study.

III. To determine the immunologic response experienced by patients who have received the peptide vaccination, as measured by changes in T-cell precursors from before to after treatment.

IV. To evaluate the quality of life of patients before and after high-dose IL-2.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive aldesleukin intravenously (IV) over 15 minutes every 8 hours for 12 doses.

ARM II: Patients receive gp100 antigen emulsified in Montanide ISA-51 subcutaneously (SC) on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2.

In both arms, treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.

After completion of treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Eligibility criteria: Inclusion Criteria:

* Any patient with measurable metastatic (stage IV or locally advanced stage III) cutaneous melanoma and an expected survival of greater than three months will be considered
* Serum creatinine of 1.6 mg/dl or less
* Total bilirubin 1.6 mg/dl or less
* White blood cell (WBC) 3000/mm\^3 or greater
* Platelet count 90,000 mm\^3 or greater
* Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less then three times normal
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Patients of both genders must be willing to practice effective birth control during this trial
* Pathologic confirmation of cutaneous melanoma; patients may enter the study with a pathologic diagnosis of cutaneous melanoma from any institution; all slides will be reviewed at National Institutes of Health (NIH) (department of Anatomic Pathology) and if the diagnosis is not confirmed, the patient will be excluded from the study
* Tissue type human leukocyte antigen (HLA) A0201

Exclusion Criteria:

* Patients who have types of melanoma other than cutaneous, i.e. ocular or mucosal
* Patients who are undergoing or have undergone in the past 4 weeks any other form of therapy except surgery for their cancer, including radiation therapy to any site
* Patients who have active systemic infections, coagulation disorders, autoimmune disease or history of other major medical illnesses such as insulin dependent diabetes mellitus, cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary diseases and inflammatory bowel disorders
* Patients who have significant psychiatric disease which in the opinion of the principal investigator would prevent adequate informed consent or render immunotherapy unsafe or contraindicated
* Patients who require steroid therapy or steroid-containing compounds, or have used systemic steroids in the past 4 weeks, or have used topical or inhalational steroids in the past 2 weeks
* Patients who are pregnant
* Patients who are known to be positive for viral hepatitis B or C (hepatitis B surface antigen \[HBsAg\] or anti hepatitis C virus \[HCV\]) or human immunodeficiency virus (HIV) (HIV antibody)
* Patients who have any form of primary or secondary immunodeficiency
* Patients who have received previous high dose IL-2 (\> 600,000 IU/kg)
* Patients who have received previous gp100 vaccines
* Patients who have an abnormal stress cardiac test (stress thallium, stress multi gated acquisition scan \[MUGA\], dobutamine echocardiogram or other stress test that will rule out cardiac ischemia)
* Patients who have abnormal pulmonary function tests (forced expiratory volume in one second \[FEV1\] \< 65% or forced vital capacity \[FVC\] \< 65% of predicted)
* Patients who have brain metastasis or history of brain metastasis
* No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years

Primary outcomes:
measure: Best Response Rate (Partial Response [PR] + Complete Response [CR])
timeFrame: Up to 12 years
Secondary outcomes:
measure: Progression Free Survival
timeFrame: From the date of randomization until documentation of progression or last follow up, assessed up to 12 years
measure: Change in T-cell Precursors
timeFrame: Baseline to up to 12 years
measure: Change in Quality of Life (QOL) Score Assessed by the FACT-G (Functional Assessment of Cancer Therapy- General), FACT-F (Functional Assessment of Cancer Therapy- Fatigue), SF-36 (Short Form 36) and SDS (Symptom Distress Scale)
timeFrame: Baseline to up to 8 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Riverside
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center - Anschutz Cancer Pavilion
state: Colorado
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital.
state: Illinois
city: Goshen
country: United States
facility: IU Health Goshen Center for Cancer Care
state: Indiana
city: Louisville
country: United States
facility: The James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: Bethesda
country: United States
facility: National Institutes of Health
state: Maryland
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Bethlehem
country: United States
facility: Saint Luke's University Hospital-Bethlehem Campus
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: IU Health Goshen Center for Cancer Care
name: Douglas Schwartzentruber
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, Gailani F, Riley L, Conlon K, Pockaj B, Kendra KL, White RL, Gonzalez R, Kuzel TM, Curti B, Leming PD, Whitman ED, Balkissoon J, Reintgen DS, Kaufman H, Marincola FM, Merino MJ, Rosenberg SA, Choyke P, Vena D, Hwu P. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011 Jun 2;364(22):2119-27. doi: 10.1056/NEJMoa1012863.