Clinical trial NCT00514085: Interleukin-21 in Treating Patients With Metastatic or Recurrent Malignant Melanoma
Official title: A Phase II Study of Interleukin-21 (IL-21) in Patients With Metastatic or Recurrent Malignant Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma (Skin)
Keywords: recurrent melanoma
stage IV melanoma
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: ZymoGenetics
First posted: 2007-08-09
Enrollment: 40
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: 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.

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 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

Primary outcomes:
measure: Objective tumor response as assessed by RECIST
timeFrame: after completion of treatment
measure: Overall response rate (complete and partial)
timeFrame: after completion of study
measure: Stable disease rate
timeFrame: after completion of study
measure: Progressive disease rate
timeFrame: after completion of study
measure: Median time to progression
timeFrame: after completion of study
measure: Response duration (median and range)
timeFrame: after completion of study
Secondary outcomes:
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Surrey
country: Canada
facility: BCCA - Fraser Valley Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
Study officials:
affiliation: Toronto Sunnybrook Regional Cancer Centre
name: Teresa M. Petrella
role: STUDY_CHAIR
References:
citation: Petrella TM, Tozer R, Belanger K, Savage KJ, Wong R, Smylie M, Kamel-Reid S, Tron V, Chen BE, Hunder NN, Hagerman L, Walsh W, Eisenhauer EA. Interleukin-21 has activity in patients with metastatic melanoma: a phase II study. J Clin Oncol. 2012 Sep 20;30(27):3396-401. doi: 10.1200/JCO.2011.40.0655. Epub 2012 Aug 20.