Interleukin-21 in Treating Patients With Metastatic or Recurrent Malignant Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00514085
First received: August 8, 2007
Last updated: July 5, 2012
Last verified: July 2012
  Purpose

RATIONALE: Interleukin-21 may stimulate white blood cells, including natural killer cells, to kill melanoma cells.

PURPOSE: This phase II trial is studying the side effects and how well interleukin-21 works in treating patients with metastatic or recurrent malignant melanoma.


Condition Intervention Phase
Melanoma (Skin)
Biological: recombinant human interleukin-21
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Interleukin-21 (IL-21) in Patients With Metastatic or Recurrent Malignant Melanoma

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Objective tumor response as assessed by RECIST [ Time Frame: after completion of treatment ] [ Designated as safety issue: No ]
  • Overall response rate (complete and partial) [ Time Frame: after completion of study ] [ Designated as safety issue: No ]
  • Stable disease rate [ Time Frame: after completion of study ] [ Designated as safety issue: No ]
  • Progressive disease rate [ Time Frame: after completion of study ] [ Designated as safety issue: No ]
  • Median time to progression [ Time Frame: after completion of study ] [ Designated as safety issue: No ]
  • Response duration (median and range) [ Time Frame: after completion of study ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: July 2007
Study Completion Date: July 2012
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: recombinant human interleukin-21

    Patients enrolled in Part A will receive treatment daily x 5 on weeks 1, 3, and 5 of an 8 week cycle.

    Patients enrolled in Part B will receive treatment daily x 5 on weeks 1, and 3 of a 6 week cycle

    Other: immunohistochemistry staining method
    Cycle 1 Day 1 and Cycle 1 Day 29
    Other: laboratory biomarker analysis
    slides will be blocked for 15 minutes in 20% normal goat serum and then incubated in primary antibody
    Other: pharmacological study
    Starting dose of 50μg/kg/day as an IV push
Detailed Description:

OBJECTIVES:

Primary

  • To assess the efficacy, in terms of objective response rate, nonprogression rate, time to progression, and response duration, in patients with metastatic or recurrent malignant melanoma treated with recombinant human interleukin-21 (rIL-21).
  • To assess the toxicity and safety of rIL-21 in patients with previously untreated metastatic or recurrent malignant melanoma.
  • To characterize the pharmacokinetics of rIL-21.
  • To characterize the effects of rIL-21 on lymphocyte cell count and soluble CD25 (sCD25) in serum as potential biomarkers for drug activity.
  • To evaluate the immunogenicity of rIL-21, specifically preexisting immunogenicity to the drug and antibody induction during treatment.
  • To assess melanoma antigenic markers for response and nonprogression on archival tissue from patients enrolled on the study.

Secondary

  • To investigate whether rIL-21 induced sCD25 release is independent of the level of circulating sCD25.
  • To investigate the effect of rIL-21 on antibody induction during treatment and preexisting immunogenicity.
  • To assess lymphocyte cell-count changes over time in relation to rIL-21 therapy.

OUTLINE: This is a multicenter study.

Patients receive recombinant human interleukin-21 (rIL-21) IV on days 1-5 of weeks 1, 3 and 5. Treatment repeats every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) or partial response (PR) receive 2 courses beyond CR or PR. Patients with stable disease receive a maximum of 3 courses of rIL-21.

Previously archived tumor tissue and blood samples are collected from patients for correlative studies. Samples are analyzed for soluble CD25, rIL-21 antibodies, circulating lymphocyte counts, preexisting immonogenicity to rIL-21 for antibody induction, and expression of common melanoma tumor antigen markers via IHC.

After completion of study treatment, patients are followed at 4 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed cutaneous malignant melanoma

    • Recurrent or metastatic disease that is not curable by surgical or other means
  • Clinically and/or radiologically documented disease defined as at least one site of disease unidimensionally measurable ≥ 20 mm by x-ray, physical exam, or nonspiral CT scan OR ≥ 10 mm by spiral CT scan
  • Must have nonbulky metastatic disease defined as the largest measurable lesion ≤ 50 mm in maximum diameter
  • Must have primary diagnosis tumor tissue or previously resected metastatic melanoma tissue available (i.e., paraffin block or unstained slides)
  • No known brain metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • Absolute granulocytes count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin normal
  • Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during study therapy
  • No uncontrolled intercurrent illness or condition including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situation that would limit compliance with study requirements
  • No history of hemolysis or a hemolytic disorder including, but not limited to, any of the following:

    • Sickle cell anemia
    • Thalassemia
    • Autoimmune hemolytic anemia
  • No history of other malignancies within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other solid tumors curatively treated with no evidence of disease
  • No known HIV, hepatitis B, or hepatitis C infection
  • Patients must reside within a 2-hour drive from a participating center

PRIOR CONCURRENT THERAPY:

  • No previous systemic therapy for metastatic disease
  • At least 3 months since prior adjuvant immunotherapy for recurrent melanoma

    • No prior immunotherapy for metastatic disease
    • No prior immunotherapy outside the adjuvant setting
  • At least 4 weeks since prior major surgery
  • At least 4 weeks since prior radiotherapy except low-dose, nonmyelosuppressive radiotherapy and recovered
  • More than 4 weeks since prior and no concurrent investigational agents or anticancer therapy
  • No prior chemotherapy including regional therapy
  • No concurrent systemic corticosteroids (e.g., prednisone or dexamethasone)

    • Concurrent topical steroids are allowed
  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: NCT00514085

Locations
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA - Fraser Valley Cancer Centre
Surrey, British Columbia, Canada, V3V 1Z2
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
CHUM - Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Teresa M. Petrella Edmond Odette Cancer Centre at Sunnybrook
  More Information

Additional Information:
No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00514085     History of Changes
Other Study ID Numbers: I189, CAN-NCIC-IND189, IND.189, ZYMOGENETICS-CAN-NCIC-IND189, CDR0000560973
Study First Received: August 8, 2007
Last Updated: July 5, 2012
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
recurrent melanoma
stage IV melanoma

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

ClinicalTrials.gov processed this record on September 18, 2014