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

Melanoma (Skin) Clinical Trial

Official title:

A Phase II Study of Interleukin-21 (IL-21) in Patients With Metastatic or Recurrent Malignant Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00514085
• Other study ID #: I189
• Secondary ID: CAN-NCIC-IND189I
• Status: Completed
• Phase: Phase 2
• Start date: December 13, 2007
• Est. completion date: July 4, 2012

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 4, 2012
• Est. primary completion date: September 2, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

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
• laboratory biomarker analysis
slides will be blocked for 15 minutes in 20% normal goat serum and then incubated in primary antibody
• pharmacological study
Starting dose of 50µg/kg/day as an IV push

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Odette Cancer Centre	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	ZymoGenetics

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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(2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective tumor response as assessed by RECIST		after completion of treatment
Primary	Overall response rate (complete and partial)		after completion of study
Primary	Stable disease rate		after completion of study
Primary	Progressive disease rate		after completion of study
Primary	Median time to progression		after completion of study
Primary	Response duration (median and range)		after completion of study