Melanoma (Skin)
Conditions
Keywords
stage II melanoma, stage III melanoma
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.
Interventions
BIOLOGICALinterferon alfa-2b
Given IV
OTHERobservation
Patients undergo observation for 4 weeks.
Sponsors
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
SWOG Cancer Research Network
Cancer and Leukemia Group B
NCIC Clinical Trials Group
Children's Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Canada, South Africa, United States
Contacts
STUDY_CHAIRSanjiv S. Agarwala, MD
St. Luke's Cancer Network at St. Luke's Hospital
STUDY_CHAIRJohn M. Kirkwood, MD
UPMC Cancer Center at UPMC Presbyterian
STUDY_CHAIRLawrence E. Flaherty, MD
Barbara Ann Karmanos Cancer Institute
STUDY_CHAIRWilliam E. Carson, MD
Ohio State University Comprehensive Cancer Center
STUDY_CHAIRMichael Smylie, MD, MB, ChB
Cross Cancer Institute at University of Alberta
PRINCIPAL_INVESTIGATORAlberto S. Pappo, MD
Texas Children's Cancer Center
Participant flow
Recruitment details
The study was activated on December 22, 1998, accrued its first patient on March 25, 1999, and closed to accrual on October 26, 2010 with final accrual of 1150 patients
Participants by arm
| Arm | Count |
|---|---|
| Observation Patients undergo observation for 4 weeks. | 569 |
| Interferon Alfa-2b Patients receive high-dose interferon alfa-2b IV over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity.
interferon alfa-2b: Given IV | 581 |
| Total | 1,150 |
Baseline characteristics
| Characteristic | Observation | Interferon Alfa-2b | Total |
|---|---|---|---|
| Age, Continuous | 52 years | 52 years | 52 years |
| Sex/Gender, Customized Female | 248 participants | 244 participants | 492 participants |
| Sex/Gender, Customized Male | 320 participants | 336 participants | 656 participants |
| Sex/Gender, Customized Missing | 1 participants | 1 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| other Total, other adverse events | 74 / 439 | 558 / 568 |
| serious Total, serious adverse events | 20 / 439 | 325 / 568 |
Outcome results
Primary
5-year Relapse-free Survival Rate
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.
Time frame: assessed every 3 months for 2 years, every 6 months for 3 years
Population: all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Observation | 5-year Relapse-free Survival Rate | 0.70 proportion of participants |
| Interferon Alfa-2b | 5-year Relapse-free Survival Rate | 0.70 proportion of participants |
p-value: 0.964Log Rank
Secondary
5-year Overall Survival Rate
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.
Time frame: assessed every 3 months for 2 years, every 6 months for 3 years
Population: all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Observation | 5-year Overall Survival Rate | 0.83 proportion of participants |
| Interferon Alfa-2b | 5-year Overall Survival Rate | 0.83 proportion of participants |
p-value: 0.558Log Rank