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Interferon Alfa-2b in Treating Patients With Melanoma and Early Lymph Node Metastasis

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ClinicalTrials.gov Identifier: NCT00004196
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : January 20, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE January 21, 2000
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date January 20, 2014
Study Start Date  ICMJE October 1999
Actual Primary Completion Date October 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00004196 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Interferon Alfa-2b in Treating Patients With Melanoma and Early Lymph Node Metastasis
Official Title  ICMJE A Multicenter Trial of Adjuvant Interferon Alfa-2b for Melanoma Patients With Early Lymph Node Metastasis Detected by Lymphatic Mapping and Sentinel Lymph Node Biopsy
Brief Summary

RATIONALE: Interferon alfa-2b may interfere with the growth of cancer cells.

PURPOSE: Randomized phase III trial to study the effectiveness of interferon alfa-2b in treating patients who have melanoma with early lymph node metastasis.

Detailed Description

OBJECTIVES:

  • Compare the efficacy of regional lymphadenectomy with or without adjuvant high-dose interferon alfa-2b on disease-free survival and overall survival of patients with invasive cutaneous melanoma with early or submicroscopic sentinel lymph node metastasis detected by histology or immunohistochemistry or by polymerase chain reaction (PCR).
  • Compare the effect of lymphadenectomy vs observation on disease-free survival and overall survival of patients with submicroscopic sentinel lymph node metastasis detected only by PCR.
  • Determine the recurrence rate and survival of patients with submicroscopic sentinel lymph node metastasis detected only by PCR.
  • Determine the positive and negative predictive value of reverse transcriptase PCR analysis of sentinel lymph nodes and peripheral blood to identify patients at risk for recurrence and death.

OUTLINE: This is a randomized, multicenter study. Patients in the randomized portions of Protocols A and B are stratified according to tumor thickness (1-2 mm vs 3-4 mm vs greater than 4 mm) and tumor ulceration (yes vs no).

All patients undergo wide local tumor excision with lymphatic mapping and sentinel node biopsy. Patients with tumors with ambiguous drainage patterns undergo lymphoscintigraphy prior to tumor excision. Patients with evidence of metastatic melanoma in the sentinel node(s) by routine histology, serial sectioning, or immunohistochemistry and who have undergone a prior regional lymph node dissection proceed to protocol A.

  • Protocol A: Patients with metastasis in a single sentinel node with no evidence of extracapsular extension and no metastatic disease in nonsentinel nodes are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive adjuvant high-dose interferon alfa-2b IV 5 days a week for 4 weeks, then subcutaneously 3 times a week for 48 weeks.
    • Arm II: Patients undergo observation. Patients with metastases in more than one sentinel node with evidence of extracapsular extension or metastasis in any nonsentinel node receive adjuvant high-dose interferon alfa-2b as in arm I.

Patients with no evidence of sentinel node(s) metastases by routine histology, serial sectioning, and immunohistochemistry and are negative by polymerase chain reaction (PCR) analysis are observed.

  • Protocol B: Patients with positive sentinel node(s) by PCR analysis are randomized to one of three treatment arms.

    • Arm I: Patients undergo observation.
    • Arm II: Patients undergo lymph node dissection.
    • Arm III: Patients undergo lymph node dissection followed by adjuvant high-dose interferon alfa-2b IV 5 days a week for 4 weeks.

Patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 3,000 patients will be accrued for this study within 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Melanoma (Skin)
Intervention  ICMJE
  • Biological: recombinant interferon alfa
  • Procedure: lymphangiography
  • Drug: Observation
Study Arms  ICMJE
  • Experimental: AI
    Patients with metastasis in a single sentinel node with no evidence of extracapsular extension and no metastatic disease in nonsentinel nodes are randomized to 1 of 2 treatment arms. Patients receive adjuvant high-dose interferon alfa-2b IV 5 days a week for 4 weeks, then subcutaneously 3 times a week for 48 weeks
    Intervention: Biological: recombinant interferon alfa
  • Experimental: Arm AII
    Patients with metastasis in a single sentinel node with no evidence of extracapsular extension and no metastatic disease in nonsentinel nodes are randomized to 1 of 2 treatment arms. Observational arm: Patients with metastases in more than one sentinel node with evidence of extracapsular extension or metastasis in any nonsentinel node receive adjuvant high-dose interferon alfa-2b as in arm AI.
    Interventions:
    • Biological: recombinant interferon alfa
    • Drug: Observation
  • Experimental: Arm BI
    Patients with positive sentinel node(s) by PCR analysis are randomized to one of three treatment arms. Patients undergo observation. Patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.
    Intervention: Drug: Observation
  • Experimental: Arm B II
    Patients with positive sentinel node(s) by PCR analysis are randomized to one of three treatment arms. Patients undergo lymph node dissection. Patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.
    Intervention: Procedure: lymphangiography
  • Experimental: Arm BIII

    Patients with positive sentinel node(s) by PCR analysis are randomized to one of three treatment arms. Patients undergo lymph node dissection followed by adjuvant high-dose interferon alfa-2b IV 5 days a week for 4 weeks.

    Patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

    Interventions:
    • Biological: recombinant interferon alfa
    • Procedure: lymphangiography
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: January¬†16,¬†2014)
3000
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE November 2007
Actual Primary Completion Date October 2004   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive cutaneous melanoma

    • Breslow thickness at least 1.0 mm
    • Primary site must be on head, neck, trunk or extremity
    • No more than 90 days since biopsy
  • Protocol A:

    • One or more sentinel lymph nodes with histologic or immunohistochemical evidence of metastatic melanoma
    • Prior regional lymph node dissection
  • Protocol B:

    • Sentinel lymph nodes with no histologic or immunohistochemical evidence of metastatic melanoma
    • Sentinel lymph node positive by reverse transcriptase polymerase chain reaction
  • No prior wide local excision of the primary tumor with a margin greater than 1.5 cm
  • No primary melanoma involving the eye or mucous membranes
  • No clinical evidence of satellite lesions or intransit, regional nodal, or distant metastases
  • No second primary invasive melanoma
  • No prior surgery in the region of the primary draining nodal basin that would disrupt normal lymphatic drainage patterns (e.g., skin grafts, tissue transfers or flaps, or lymph node dissections)

PATIENT CHARACTERISTICS:

Age:

  • 18 to 70

Performance status:

  • Karnofsky 70-100%

Life expectancy:

  • At least 10 years

Hematopoietic:

  • WBC at least 3,000/mm^3
  • Absolute granulocyte count at least 1,500/mm^3
  • Platelet count at least 70,000/mm^3
  • Hemoglobin at least 10.0 g/dL

Hepatic:

  • Bilirubin less than 2.0 mg/dL
  • SGOT/SGPT less than 3 times upper limit of normal (ULN)
  • Alkaline phosphatase less than 3 times ULN
  • No severe decompensated liver disease (e.g., cirrhosis or autoimmune hepatitis)
  • No other significant liver disease that would preclude study participation

Renal:

  • Creatinine normal

Cardiovascular:

  • No cardiovascular disease (e.g., angina or congestive heart failure)
  • No myocardial infarction within the past year
  • No tachyarrhythmias

Pulmonary:

  • No severe debilitating pulmonary disease (e.g., chronic obstructive pulmonary disease)

Other:

  • No hypersensitivity to interferon alfa-2b or related compounds or any component of the injection
  • No major depression or other major psychiatric illness
  • No thyroid disorder with thyroid function that is not maintained within the normal range with medications
  • No autoimmune disease
  • No primary or secondary immunodeficiencies
  • No severe diabetes mellitus prone to ketoacidosis
  • No significant retinal abnormalities
  • No evidence of infection
  • No other malignancy within the past 5 years except basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I laryngeal cancer
  • No other medical condition that would preclude study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after the study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior immunotherapy

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • At least 6 months since prior oral or parenteral steroids

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • See Disease Characteristics
  • No prior organ transplantation

Other:

  • At least 6 months since prior immunosuppressants
  • No concurrent immunosuppressants resulting from prior organ transplantation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00004196
Other Study ID Numbers  ICMJE CDR0000067439
UAB-9735
UAB-F970925009
NCI-G99-1654
RPCI-DS-99-14
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Marshall M. Urist, MD University of Alabama at Birmingham
PRS Account University of Alabama at Birmingham
Verification Date April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP