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S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma

Phase 3
Completed
Conditions
Melanoma (Skin)
Interventions
Biological: interleukin-2
Biological: filgrastim
Biological: interferon alfa
Registration Number
NCT00006237
Lead Sponsor
SWOG Cancer Research Network
Brief Summary

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.

Detailed 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
432
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm IIfilgrastimPatients 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.
Arm IIinterferon alfaPatients 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.
Arm Iinterferon alfaPatients 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 IIinterleukin-2Patients 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.
Arm IIcisplatinPatients 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.
Arm IIdacarbazinePatients 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.
Arm IIvinblastinePatients 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.
Primary Outcome Measures
NameTimeMethod
5-year Overall SurvivalEvery three months for a year, every six months for years 2-5, annual for years 5-10

Overall survival was measured from the date of registration to study until death from any cause with observations censored at the date of last contact for patients last known to be alive.

5-year Relapse-Free SurvivalEvery three months for the first year, every 6 months for years 2-5, annually for years 6-10

Measured from date of registration to date of first observation of progressive disease or death due to any cause.

Secondary Outcome Measures
NameTimeMethod
ToxicityWhile on treatment, patients on the HDIFN arm were assessed weekly for the 1st month, then every 2 weeks for the 2nd month, then every 3 months therafter; patients on the biochemo arm were assessed daily for the 1st 5 days, then weekly thereafter.

Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event

Trial Locations

Locations (296)

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

🇺🇸

Birmingham, Alabama, United States

Mobile Infirmary Medical Center

🇺🇸

Mobile, Alabama, United States

Banner Thunderbird Medical Center

🇺🇸

Glendale, Arizona, United States

Banner Good Samaritan Medical Center

🇺🇸

Phoenix, Arizona, United States

CCOP - Western Regional, Arizona

🇺🇸

Phoenix, Arizona, United States

Phoenix Children's Hospital

🇺🇸

Phoenix, Arizona, 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

🇺🇸

Ft. Smith, Arkansas, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Eden Medical Center

🇺🇸

Castro Valley, California, United States

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Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
🇺🇸Birmingham, Alabama, United States
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