S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
RATIONALE: Interferon alfa may interfere with the growth of cancer cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known whether interferon alfa is more effective with or without combination chemotherapy and interleukin-2 for melanoma.
PURPOSE: Randomized phase III trial to compare the effectiveness of interferon alfa with or without combination chemotherapy consisting of cisplatin, vinblastine, and dacarbazine, plus interleukin-2, in treating patients who have melanoma.
Full description
OBJECTIVES:
- Compare the overall survival and disease-free survival of patients with high-risk melanoma treated with interferon alfa vs cisplatin, vinblastine, and dacarbazine plus interferon alfa and interleukin-2.
- Compare the toxic effects of these treatment regimens in these patients.
- Determine the relationship between minimal residual disease (MRD) status at 12 weeks and 52 weeks and overall survival of patients treated with these regimens.
- Compare the effects of these treatment regimens on the MRD status of these patients.
- Determine the relationship between clinical characteristics (number of involved lymph nodes, ulcerated primary, and extracapsular extension) and MRD in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to nodal status (N1 or N2 vs N3), degree of lymph node involvement (micrometastases only vs any macrometastases, including satellite/in-transit metastases), and ulceration of the primary tumor (yes vs no vs unknown primary). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive interferon alfa IV on days 1-5 of weeks 1-4 followed by interferon alfa subcutaneously (SC) on days 1, 3, and 5 of weeks 5-52 in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive cisplatin IV over 30 minutes followed by vinblastine IV on days 1-4. Patients also receive dacarbazine IV over 1 hour on day 1, interleukin-2 IV over 96 hours on days 1-4, and interferon alfa SC on days 1-5, 8, 10, and 12. In addition, patients receive filgrastim (G-CSF) SC on days 6-15. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.
PROJECTED ACCRUAL: A total of 410 patients (205 per treatment arm) will be accrued for this study within 3 years.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
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Histologically proven melanoma of cutaneous origin or from unknown primary at initial presentation of primary or first clinically detected nodal or satellite/in-transit recurrence
- No distant metastases
- No melanoma of ocular, mucosal, or other non-cutaneous origin
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One of the following criteria must apply for patients with newly diagnosed melanoma OR a previously diagnosed primary with current subsequent, clinical, regional nodal disease and/or satellite/in-transit disease:
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Ulcerated primary melanoma with 1 or more involved lymph nodes (micro/occult or macro/clinically overt)
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Non-ulcerated or unknown primary melanoma with one macro/clinically overt lymph node metastasis, including a single matted nodal mass
- No non-ulcerated or unknown primary tumor and a single micrometastatic lymph node
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Non-ulcerated melanoma with two or more lymph node metastases (micro/occult or macro/clinically overt) and/or matted nodes
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Any satellite/in transit metastasis with or without lymph node involvement
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Patients with recurrent disease must have recurrent disease in the regional nodal basin of a prior complete lymphadenectomy
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Multiple regional nodal basin involvement allowed if they are appropriate anatomic drainage basins for primary site
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Patients must be disease free at time of enrollment based on the following surgical criteria:
- Patients at initial presentation of melanoma must undergo adequate wide excision of primary lesion
- Patients with previously diagnosed melanoma must have all disease resected with pathologically negative margins and no disease at primary site or second resection of primary
- Full lymphadenectomy required of all patients including those with positive sentinel nodes or positive satellite/in-transit metastasis
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No more than 56 days since prior lymphadenectomy OR surgery to remove recurrent disease after prior complete lymphadenectomy
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Must be willing to participate in minimal residual disease studies if registered on the study on 3/1/2003 or later
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Zubrod 0-1
Life expectancy:
- Not specified
Hematopoietic:
- Absolute granulocyte count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- SGOT or SGPT no greater than 2 times ULN
- LDH and alkaline phosphatase no greater than 2 times ULN (above normal value requires a contrast-enhanced CT scan or MRI of liver)
- No known recent hepatitis positivity by PCR
Renal:
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance at least 75 mL/min
Cardiovascular:
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No congestive heart failure
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No coronary artery disease
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No serious cardiac arrhythmia
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No prior myocardial infarction
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Normal cardiac stress test required if any of the following are present:
- Over age 50
- Abnormal EKG
- History of cardiac disease
Pulmonary:
- No symptomatic pulmonary disease
Other:
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective contraception
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No autoimmune disorders or conditions of immunosuppression
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No other prior malignancy within the past 5 years except the following:
- Adequately treated basal cell or squamous cell skin cancer
- Carcinoma in situ of the cervix
- Adequately treated stage I or II cancer in remission
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HIV negative
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No known AIDS or HIV-1 associated complex
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No prior immunotherapy, including interferon, interleukin, levamisole, or other biologic response modifiers
- No other concurrent biologic therapy
Chemotherapy:
- No prior chemotherapy (including infusion or perfusion therapy)
- No other concurrent chemotherapy
Endocrine therapy:
- No concurrent systemic corticosteroids or topical steroid creams
- Concurrent steroid antihistamines allowed if no alternative
- No concurrent hormonal therapy
Radiotherapy:
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No prior radiotherapy
- Prior postlumpectomy radiotherapy for breast cancer allowed
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No concurrent radiotherapy
Surgery:
- See Disease Characteristics
- No concurrent surgery
Other:
- No concurrent anti-hypertensive medications (arm II only)
- No concurrent immunosuppressive agents
- No other concurrent anticancer therapy
- Antihistamines allowed if no alternative medication suitable
Trial design
Primary purpose
Allocation
Interventional model
Masking
432 participants in 2 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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