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

• Sponsor: Eastern Cooperative Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Eastern Cooperative Oncology Group

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Melanoma (Skin)	Biological: PEG-interferon alfa-2b	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	32 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase II Study of Low Dose Peginterferon Alfa-2b in Patients With Metastatic Melanoma Over-Expressing Basic Fibroblast Growth Factor
Study Start Date :	September 2003
Actual Primary Completion Date :	August 2012
Actual Study Completion Date :	June 2014

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Plasma b-FGF Level Response [ Time Frame: 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 ]
   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.

Secondary Outcome Measures :

1. Non-progression Rate (Clinical Response to Peginterferon Alfa-2b) [ Time Frame: 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 ]

   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.

2. Progression Free Survival [ Time Frame: 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 (PFS) was defined as the time from registration to disease progression, or censored at last known date of non progressive disease.
3. Overall Survival [ Time Frame: assessed every 3 months if <2 years, and every 6 months if 2-3 years ]
   Overall survival (OS) time was defined as the time from registration to death from any cause, or censored at last known date of survival.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

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Study Chair:	Ronald S. Go, MD	Gundersen Lutheran Center for Cancer and Blood

More Information

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Responsible Party:	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00049530 History of Changes
Other Study ID Numbers:	CDR0000258114; E2602 ( Other Identifier: Eastern Cooperative Oncology Group ); U10CA021115 ( U.S. NIH Grant/Contract )
First Posted:	January 27, 2003
Results First Posted:	June 3, 2014
Last Update Posted:	October 28, 2015
Last Verified:	May 2014

Keywords provided by Eastern Cooperative Oncology Group:

recurrent melanoma; stage IV melanoma

Additional relevant MeSH terms:

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Melanoma; Nevi and Melanomas; Interferons; Interferon alpha-2; Interferon-alpha; Peginterferon alfa-2b; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type	Neoplasms; Neoplasms, Nerve Tissue; Mitogens; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Physiological Effects of Drugs