High-Dose Interferon Alfa in Treating Patients With Stage II or Stage III Melanoma

Phase 3

Active, not recruiting

Conditions: Melanoma (Skin)

Registration Number: NCT00003641

Lead Sponsor: ECOG-ACRIN Cancer Research Group

Brief Summary: RATIONALE: Interferon alfa may interfere with the growth of cancer cells. It is not yet known whether treatment with interferon alfa is more effective than observation alone for stage II or stage III melanoma that has been completely removed surgically.

PURPOSE: This randomized phase III trial is studying high dose interferon alfa to see how well it works compared to observation only in treating patients with stage II or stage III melanoma that has been completely removed by surgery.

Detailed Description: OBJECTIVES:

Primary Objective:

* Compare the effect of high-dose interferon alfa-2b treatment on the relapse-free survival of patients with stage II or III resected malignant melanoma.

Secondary Objectives:

* Compare the effect of this treatment regimen on overall survival of these patients.

* Assess the toxicity of this treatment in these patients.

* Compare the effect of treatment on quality of life.

OUTLINE: This is a randomized study. Patients are stratified by pathologic lymph node status (known vs unknown),lymph node staging procedures(sentinel lymph node procedure vs. elective lymph node dissection vs. no lymphadenectomy), Breslow depth (\<= 1.0 mm vs. 1.01-2.0 mm vs. 2.01-4.0 mm vs \> 4.0 mm), ulceration of the primary lesion (yes vs. no vs. unknown), and disease stage (lymph node positive \[N1, N2a\] vs. lymph node negative \[N0\]). Patients are randomized into one of two treatment arms in a 1:1 ratio.

* Arm I (observation): Patients undergo observation for 4 weeks.

* Arm II (Interferon Alfa-2b): Patients receive high-dose interferon alfa-2b intravenously (IV) over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity.

Quality of life is assessed before treatment, at day 22, every 3 months for 2 years, and then every 6 months for 3 years.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter until 15 years after randomization.

PROJECTED ACCRUAL: A total of 1,420 patients will be accrued for this study over 5 years.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 1150

Inclusion Criteria

Histologically confirmed primary melanoma of cutaneous origin
- Stage II (T3 N0 M0 1.5-4.0 mm Breslow depth)
  - Clinically negative regional lymph node pathologic status unknown OR
  - Histologically negative regional lymph nodes
- Stage III (T4 N0 M0)
  - Greater than 4.0 mm Breslow depth OR
- Stage III (T1-4 N1)
  - One lymph node positive microscopically
Patients must meet at least 1 of the following criteria:
- T2b N0 - primary melanoma 1.01-2.0 mm with ulceration, node negative
- T3a-b N0 - primary melanoma 2.01-4.0 mm with and without ulceration, node negative
- T4a-b N0 - primary melanoma > 4.0 mm with or without ulceration, node negative
- T1a N1a-2a (microscopic) - primary melanoma of any thickness with microscopically positive lymph node (any number)
Patients with a positive sentinel node should undergo complete lymphadenectomy of the nodal basin prior to study
Must complete all primary therapy (wide excision with or without lymphadenectomy) and be randomized in this study within 84 days of wide excision
Must have undergone an adequate wide excision of the primary lesion
Age 18 and over (For ECOG patients only, patients must be >=10 years)
Eastern Cooperative Oncology Group (ECOG) Performance status of 0-1
Adequate hematopoietic, hepatic, and renal function based on the following tests:
- White blood cell (WBC) cout at least 3,000/mm^3
- Platelet count at least 125,000/mm^3
- Hematocrit at least 30%
- Bilirubin no greater than 2 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase no greater than 2 times ULN
- If lactate dehydrogenase or alkaline phosphatase is above normal, a contrast-enhanced computed tomography (CT) scan or Magnetic resonance imaging (MRI) of the liver is required to document the absence of tumor
- Blood urea nitrogen (BUN) no greater than 33 mg/dL OR Creatinine no greater than 1.8 mg/dL
No other concurrent or prior malignancies within the past 5 years except:
- Cancer in situ
- Lobular carcinoma in situ of the breast
- Carcinoma in situ of the cervix
- Atypical melanocytic hyperplasia or Clark 1 melanoma in situ
- Basal or squamous cell skin cancer
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after study

Exclusion Criteria

Clinical, radiological/laboratory, or pathological evidence of incompletely resected melanoma or any distant metastatic disease
Clinically palpable lymphadenopathy
Evidence of organic brain syndrome or significant impairment of basal cognitive function or any psychiatric disorder that would preclude study participation
Other significant medical or surgical condition, or any medication or treatment regimens, that would interfere with study participation
Pregnant or nursing
Other history of invasive melanoma
Autoimmune disorders or conditions of immunosuppression
History of active ischemic heart disease
Cerebrovascular disease
Congestive heart failure (New York Heart Association class III or IV heart disease)
Prior or concurrent chemotherapy
Prior immunotherapy including tumor vaccines, interferon, interleukins, levamisole, or other biologic response modifiers for melanoma
Concurrent systemic corticosteroids including oral steroids (i.e., prednisone, dexamethasone), topical steroid creams or ointments, or any steroid-containing inhalers
Prior or concurrent radiotherapy
Other concurrent immunosuppressive medications

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
5-year Relapse-free Survival Rate	assessed every 3 months for 2 years, every 6 months for 3 years	Relapse-free survival (RFS) was defined as time from randomization to disease relapse or death from any cause, whichever occurred first. Patients without disease relapse were censored at last disease assessment date known of free of relapse. Kaplan-Meier method was used to estimate 5-year RFS rate in the intent-to-treat (ITT) patients.

Secondary Outcome Measures

Name	Time	Method
5-year Overall Survival Rate	assessed every 3 months for 2 years, every 6 months for 3 years	Overall survival (OS) was defined as time from randomization to death from any cause. Patients still alive were censored at last known alive date. Kaplan-Meier method was used to estimate 5-year OS rate in the ITT patients.

Trial Locations

Locations (532): UAB Comprehensive Cancer Center
🇺🇸
Birmingham, Alabama, United States
University of South Alabama Mitchell Cancer Institute
🇺🇸
Mobile, Alabama, United States
Arizona Cancer Center at University of Arizona Health Sciences Center
🇺🇸
Tucson, Arizona, United States
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
🇺🇸
Fort Smith, Arkansas, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Kaiser Permanente - Deer Valley
🇺🇸
Antioch, California, United States
Alta Bates Summit Comprehensive Cancer Center
🇺🇸
Berkeley, California, United States
Peninsula Medical Center
🇺🇸
Burlingame, California, United States
Southern California Permanente Medical Group
🇺🇸
Downey, California, United States
Kaiser Permanente - Fremont
🇺🇸
Fremont, California, United States
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UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States