PEG-Interferon Alfa-2b in Treating Patients With Stage IV Melanoma

Phase II Study of Low Dose Peginterferon Alfa-2b in Patients With Metastatic Melanoma Over-Expressing Basic Fibroblast Growth Factor

RATIONALE: Peginterferon (PEG-interferon) alfa-2b may stop the growth of cancer by stopping blood flow to the tumor.

PURPOSE: Phase II trial to study the effectiveness of PEG-interferon alfa-2b in treating patients who have stage IV melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: PEG-interferon alfa-2b

Detailed Description

OBJECTIVES:

• Determine the ability of low-dose PEG-interferon alfa-2b to suppress plasma basic fibroblast growth factor (b-FGF) levels to normal in patients with metastatic melanoma over-expressing b-FGF.
• Determine the antitumor effect of this drug, in terms of progression-free and overall survival and tumor response, in these patients.
• Correlate tumor activity of this drug with b-FGF and vascular endothelial growth factor levels in the plasma and urine of these patients.
• Determine the safety profile of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study within 2 years.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Comprehensive Cancer Center
  • Florida
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Cancer Center at Lakeland Regional Medical Center
  • Illinois
    • Bloomington, Illinois, United States, 61701
      • St. Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Eureka, Illinois, United States, 61530
      • Eureka Community Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Clinic, PC
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hinsdale, Illinois, United States, 60521
      • Hinsdale Hematology Oncology Associates
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Community Hospital of Ottawa
    • Pekin, Illinois, United States, 61554
      • Cancer Treatment Center at Pekin Hospital
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61637
      • OSF St. Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • CCOP - Illinois Oncology Research Association
    • Peoria, Illinois, United States, 61615
      • Oncology Hematology Associates of Central Illinois, PC - Peoria
    • Peru, Illinois, United States, 61354
      • Illinois Valley Community Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Rockford, Illinois, United States, 61104-2315
      • Swedish-American Regional Cancer Center
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44309-2090
      • Summa Center for Cancer Care at Akron City Hospital
    • Canton, Ohio, United States, 44710-1799
      • Aultman Cancer Center at Aultman Hospital
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Cancer Care Center at MetroHealth Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Centers
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Health Sciences Center - Charleston
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Center for Cancer and Blood

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Histologically confirmed stage IV melanoma

  • Stage M1a, M1b, or M1c
  • Mucosal, ocular, or unknown primary melanoma
• Previously untreated OR received up to 3 prior systemic therapy regimens (excluding vaccine therapy) for metastatic disease
• Plasma basic fibroblast growth factor level at least 15 pg/mL
• Measurable or evaluable disease

• Central nervous system (CNS) involvement allowed provided CNS directed therapy has been given and disease has been clinically stable for ≥ 3 months

  • Brain computed tomography (CT) scan or Magnetic resonance imaging (MRI) to confirm stable disease required ≤ 4 weeks prior to study entry
• Age: 18 and over
• ECOG Performance status of 0-2
• Life expectancy at least 6 months
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 8 g/dL (transfusions allowed)
• Bilirubin no greater than 2 times upper limit of normal (ULN)
• Alanine Aminotransferase (ALT) no greater than 2 times ULN
• Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min
• At least 4 weeks since prior interferon in the adjuvant or metastatic setting
• At least 4 weeks since prior chemotherapy in the adjuvant or metastatic setting
• At least 4 weeks since prior endocrine therapy in the adjuvant or metastatic setting
• At least 4 weeks since prior radiotherapy in the adjuvant or metastatic setting
• At least 4 weeks since prior surgery in the adjuvant or metastatic setting
• At least 4 weeks since other prior therapy in the adjuvant or metastatic setting
• Negative pregnancy test
• Fertile patients must use effective contraception

Exclusion criteria:

• Myocardial infarction within the past 6 months
• Other active malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• Other concurrent illness that would preclude study participation
• History of severe depression
• Pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PEG-interferon alfa-2b; Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.

Biological: PEG-interferon alfa-2b; Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma b-FGF Level Response	The primary endpoint was the suppression of plasma b-FGF level with low dose peginterferon alfa-2b. A clinically important reduction of plasma b-FGF levels was determined to be a level less than or equal to 7.5 pg/mL. A patient was considered to have a suppressed plasma b-FGF level, if the patient experienced the clinically significant reduction (less than or equal to 7.5 pg/mL) of plasma b-FGF levels for two consecutive determinations which were at least three weeks apart. This was considered as a b-FGF response.	assessed every 3 weeks until the suppression of plasma b-FGF level to normal, then every 6 weeks until the completion of 12 months of treatment, and upon treatment discontinuation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-progression Rate (Clinical Response to Peginterferon Alfa-2b)	Objective tumor response was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Per RECIST criteria, complete response (CR) = disappearance of all target and non-target lesions. Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Progression is defined as at least 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing non-target lesions. Stable disease (SD) = did not meet criteria for response or progression. Non-progression rate = CR + PR + SD.	assessed every 9 weeks until suppression of plasma b-FGF level to normal, every 12 weeks until the completion of 12 months of treatment, >= 4 weeks after documented response. After off treatment, every 3 months if <2 years, and every 6 months if 2-3 years
Progression Free Survival	Progression free survival (PFS) was defined as the time from registration to disease progression, or censored at last known date of non progressive disease.	assessed every 9 weeks until suppression of plasma b-FGF level to normal, every 12 weeks until the completion of 12 months of treatment, >= 4 weeks after documented response. After off treatment, every 3 months if <2 years, and every 6 months if 2-3 years
Overall Survival	Overall survival (OS) time was defined as the time from registration to death from any cause, or censored at last known date of survival.	assessed every 3 months if <2 years, and every 6 months if 2-3 years

Collaborators and Investigators

• Sponsor: Eastern Cooperative Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Ronald S. Go, MD, Gundersen Lutheran Center for Cancer and Blood

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2004
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: November 12, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimated): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b
• Other Study ID Numbers: CDR0000258114; U10CA021115 (U.S. NIH Grant/Contract); E2602 (Other Identifier: Eastern Cooperative Oncology Group)