Aldesleukin With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00019682
First received: July 11, 2001
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

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 metastatic melanoma. Randomized phase III trial to compare the effectiveness of aldesleukin with or without vaccine therapy in treating patients with stage III or stage IV melanoma.


Condition Intervention Phase
Recurrent Melanoma
Stage IIIA Melanoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Stage IV Melanoma
Biological: aldesleukin
Biological: gp100 antigen
Drug: Montanide ISA 51 VG
Procedure: quality-of-life assessment
Other: questionnaire administration
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Best response rate (partial response [PR] + complete response [CR]) [ Time Frame: Up to 12 years ] [ Designated as safety issue: No ]
    The Chi-squared test will be used for evaluating differences in response rates. Stratified analyses, such as Thomas's test for combining Fisher's exact tests could be used as part of the stratified analysis as well.


Secondary Outcome Measures:
  • Progression free survival [ Time Frame: From the date of randomization until documentation of progression or last follow-up, assessed up to 12 years ] [ Designated as safety issue: No ]
    Will be compared between groups by means of Kaplan-Meier curves using the Log-Rank test to evaluate the significance of the difference between the arms.

  • Change in T-cell precursors [ Time Frame: Baseline and up to 12 years ] [ Designated as safety issue: No ]
    The change in T-cell precursors will be calculated and compared between arms using the two-sample t-test (if data are at least approximately normally distributed) or the Wilcoxon Rank Sum test, using two tailed p-values for all comparisons.

  • Change in quality of life score [ Time Frame: Baseline and 3 weeks ] [ Designated as safety issue: No ]
    A test of normality will be performed, and if the appropriate score changes are normally distributed, then a paired t-test will be used to assess the changes from pre-therapy to post-therapy; otherwise a Wilcoxon signed rank test will be used. All p-values will be two-tailed.


Enrollment: 185
Study Start Date: December 1999
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (aldesleukin)
Patients receive aldesleukin IV over 15 minutes every 8 hours for 12 doses. Treatment repeats every 3 weeks for 2 courses. 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.
Biological: aldesleukin
Given IV
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (gp100 antigen in Montanide IDA-51 and aldesleukin)
Patients receive gp100 antigen emulsified in Montanide ISA-51 subcutaneously on day 1. Patients also receive IL-2 as in arm I beginning on day 2. Treatment repeats every 3 weeks for 2 courses. 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.
Biological: aldesleukin
Given IV
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Biological: gp100 antigen
Given subcutaneously
Other Name: gp100
Drug: Montanide ISA 51 VG
Given SC
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To identify whether the addition of the peptide vaccine to high dose 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: This is a randomized, multicenter study. Patients are stratified according to disease site (cutaneous or subcutaneous only vs any other site with or without subcutaneous disease). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive aldesleukin (IL-2) IV over 15 minutes every 8 hours for 12 doses.

ARM II: Patients receive gp100 antigen emulsified in Montanide ISA-51 subcutaneously on day 1. Patients also receive IL-2 as in arm I beginning on day 2.

In both arms, treatment repeats every 3 weeks for 2 courses. 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.

Quality of life is assessed before and after the first course of IL-2.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 93-185 patients (46-93 per treatment arm) will be accrued for this study within 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • WBC 3000/mm^3 or greater
  • Platelet count 90,000 mm^3 or greater
  • Serum AST/ALT less then three times normal
  • 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 (HBsAg or Anti HCV) or 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 MUGA, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia)
  • Patients who have abnormal pulmonary function tests (FEV1 < 65% or 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00019682

Locations
United States, Indiana
Indiana University Health Goshen Center for Cancer Care
Goshen, Indiana, United States, 46526
Sponsors and Collaborators
Investigators
Principal Investigator: Douglas Schwartzentruber Indiana University Health Goshen Center for Cancer Care
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00019682     History of Changes
Obsolete Identifiers: NCT00001801
Other Study ID Numbers: NCI-2012-02897, 99-C-0051, CDR0000066963
Study First Received: July 11, 2001
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Aldesleukin
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 30, 2014