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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


Phase 3
18 Years
70 Years
Open (Enrolling)
Both
Melanoma (Skin)

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Trial Information

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


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Marshall M. Urist, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Alabama at Birmingham

Authority:

United States: Federal Government

Study ID:

CDR0000067439

NCT ID:

NCT00004196

Start Date:

October 1999

Completion Date:

Related Keywords:

  • Melanoma (Skin)
  • stage I melanoma
  • stage II melanoma
  • stage III melanoma
  • Melanoma
  • Neoplasm Metastasis

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
University of Alabama at Birmingham Comprehensive Cancer CenterBirmingham, Alabama  35294-3300
Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
James Graham Brown Cancer Center at University of LouisvilleLouisville, Kentucky  40202