S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma

This study has been completed.
Sponsor:
Collaborators:
Eastern Cooperative Oncology Group
Cancer and Leukemia Group B
Children's Oncology Group
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00006237
First received: September 11, 2000
Last updated: November 15, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Melanoma (Skin)
Biological: interleukin-2
Biological: filgrastim
Biological: interferon alfa
Drug: cisplatin
Drug: dacarbazine
Drug: vinblastine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Trial of High Dose Interferon Alfa 2-b Versus Cisplatin, Vinblastine, DTIC Plus IL-2 and Interferon in Patients With High Risk Melanoma

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 5-year Overall Survival [ Time Frame: Every three months for a year, every six months for years 2-5, annual for years 5-10 ] [ Designated as safety issue: No ]
    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 Survival [ Time Frame: Every three months for the first year, every 6 months for years 2-5, annually for years 6-10 ] [ Designated as safety issue: No ]
    Measured from date of registration to date of first observation of progressive disease or death due to any cause.


Secondary Outcome Measures:
  • Toxicity [ Time Frame: While 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. ] [ Designated as safety issue: Yes ]
    Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event


Enrollment: 432
Study Start Date: August 2000
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Biological: interferon alfa
Given IV and subcutaneously
Experimental: 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.
Biological: interleukin-2
Given IV
Other Name: aldesleukin
Biological: filgrastim
Given subcutaneously
Biological: interferon alfa
Given IV and subcutaneously
Drug: cisplatin
Given IV
Drug: dacarbazine
Given IV
Drug: vinblastine
Given IV

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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
  • 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:

    • Ulcerated primary melanoma with 1 or more involved lymph nodes (micro/occult or macro/clinically overt)
    • 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
    • Non-ulcerated melanoma with two or more lymph node metastases (micro/occult or macro/clinically overt) and/or matted nodes
    • Any satellite/in transit metastasis with or without lymph node involvement
  • Patients with recurrent disease must have recurrent disease in the regional nodal basin of a prior complete lymphadenectomy
  • Multiple regional nodal basin involvement allowed if they are appropriate anatomic drainage basins for primary site
  • 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
  • No more than 56 days since prior lymphadenectomy OR surgery to remove recurrent disease after prior complete lymphadenectomy
  • 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:

  • No congestive heart failure
  • No coronary artery disease
  • No serious cardiac arrhythmia
  • No prior myocardial infarction
  • 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:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No autoimmune disorders or conditions of immunosuppression
  • 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
  • HIV negative
  • 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:

  • No prior radiotherapy

    • Prior postlumpectomy radiotherapy for breast cancer allowed
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006237

  Show 297 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Eastern Cooperative Oncology Group
Cancer and Leukemia Group B
Children's Oncology Group
Investigators
Study Chair: Lawrence E. Flaherty, MD Barbara Ann Karmanos Cancer Institute
Principal Investigator: John A. Thompson, MD Seattle Cancer Care Alliance
Principal Investigator: John T. Vetto, MD, FACS OHSU Knight Cancer Institute
Study Chair: Michael B. Atkins, MD Beth Israel Deaconess Medical Center
Principal Investigator: John M. Kirkwood, MD University of Pittsburgh
Study Chair: Frank Haluska, MD, PhD Massachusetts General Hospital
Principal Investigator: Alberto S. Pappo, MD Texas Children's Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00006237     History of Changes
Obsolete Identifiers: NCT00546416
Other Study ID Numbers: CDR0000068162, U10CA032102, S0008, CALGB-500002, ECOG-S0008, COG-S0008
Study First Received: September 11, 2000
Results First Received: August 20, 2012
Last Updated: November 15, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
stage III melanoma
recurrent melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cisplatin
Interferons
Interleukin-2
Vinblastine
Interferon-alpha
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on October 02, 2014