Interferon Alfa Following Surgery in Treating Patients With Stage III Melanoma

• ClinicalTrials.gov Identifier: NCT00006249
• Recruitment Status: Unknown
• First Posted: January 27, 2003
• Last Update Posted: February 10, 2015
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Information provided by (Responsible Party): European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information

• First Submitted Date: September 11, 2000
• First Posted Date: January 27, 2003
• Last Update Posted Date: February 10, 2015
• Study Start Date: June 2000
• Actual Primary Completion Date: August 2003 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 19, 2012)

distant-metastasis free-survival (DMFS) [ Time Frame: from randomization ]

distant-metastasis free-survival (DMFS) after randomization

• Original Primary Outcome Measures: Not Provided
• Change History: Complete list of historical versions of study NCT00006249 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: July 19, 2012)

• survival [ Time Frame: from randomization till death ]
  duration of survival: time from randomization until death, whatever the cause
• toxicity [ Time Frame: from randomization ]
  toxicity

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: July 19, 2012)

quality of life [ Time Frame: from randomization ]

Quality of life evaluation

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Interferon Alfa Following Surgery in Treating Patients With Stage III Melanoma
• Official Title: PEG-Intron Observation After Regional Lymph Node Dissection in AJCC Stage III (TxN1-2MO) Melanoma Patients: a Randomized Phase III Trial

Brief Summary

RATIONALE: Interferon alfa may interfere with the growth of the cancer cells. It is not yet known if this treatment is more effective than observation following surgery for stage III melanoma.

PURPOSE: Randomized phase III trial to determine the effectiveness of interferon alfa in treating patients who have undergone surgery for stage III melanoma.

Detailed Description

OBJECTIVES:

• Compare the effect of adjuvant therapy with pegylated interferon alfa vs observation, in terms of distant metastases-free survival, in patients with previously resected stage III melanoma.
• Compare the overall survival in these patients after treatment with pegylated interferon alfa vs observation.
• Determine the toxicity of pegylated interferon alfa in these patients.
• Determine the compliance of these patients treated with pegylated interferon alfa.
• Compare the quality of life in these patients after treatment with pegylated interferon alfa vs observation.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to type of nodal involvement (N1 vs N2), number of positive nodes (1 vs 2-4 vs 5 or more vs not assessed), Breslow primary (T1-2 vs T3 vs T4 vs unknown), ulceration of primary tumor (absent vs present vs unknown), sex, and center. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive pegylated interferon alfa subcutaneously weekly for 5 years.
• Arm II: Patients undergo observation only. Treatment continues in the absence of distant metastases or unacceptable toxicity.

Quality of life is assessed at baseline, and then at months 3, 12, 24, 36, 48, and 60.

Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 1,200 patients (600 per treatment arm) will be accrued for this study within 1.5-2 years.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Melanoma (Skin)

Intervention

• Biological: pegylated interferon alfa
• Procedure: adjuvant therapy

Study Arms

• No Intervention: observation
  5 years observation + 5 years follow up
• Experimental: pegylated interferon alfa
  5 years pegylated interferon alfa + 5 years follow up
  Interventions:

  • Biological: pegylated interferon alfa
  • Procedure: adjuvant therapy

Publications *

• Eggermont AM, Suciu S, Testori A, Kruit WH, Marsden J, Punt CJ, Santinami M, Salès F, Schadendorf D, Patel P, Dummer R, Robert C, Keilholz U, Yver A, Spatz A. Ulceration and stage are predictive of interferon efficacy in melanoma: results of the phase III adjuvant trials EORTC 18952 and EORTC 18991. Eur J Cancer. 2012 Jan;48(2):218-25. doi: 10.1016/j.ejca.2011.09.028. Epub 2011 Nov 5.
• Eggermont AM, Suciu S, Santinami M, et al.: EORTC 18991 phase III trial: Long-term adjuvant pegylated interferon-α2b (PEG-IFN) versus observation in resected stage III melanoma: long-term results at 7.6-years follow-up. [Abstract] J Clin Oncol 29 (Suppl 15): A-8506b, 2011.
• Bouwhuis MG, Suciu S, Testori A, Kruit WH, Salès F, Patel P, Punt CJ, Santinami M, Spatz A, Ten Hagen TL, Eggermont AM. Phase III trial comparing adjuvant treatment with pegylated interferon Alfa-2b versus observation: prognostic significance of autoantibodies--EORTC 18991. J Clin Oncol. 2010 May 10;28(14):2460-6. doi: 10.1200/JCO.2009.24.6264. Epub 2010 Apr 12.
• Eggermont AM, Bouwhuis MG, Kruit WH, Testori A, ten Hagen T, Yver A, Xu C. Serum concentrations of pegylated interferon alpha-2b in patients with resected stage III melanoma receiving adjuvant pegylated interferon alpha-2b in a randomized phase III trial (EORTC 18991). Cancer Chemother Pharmacol. 2010 Mar;65(4):671-7. doi: 10.1007/s00280-009-1072-z. Epub 2009 Jul 21.
• Bottomley A, Coens C, Suciu S, Santinami M, Kruit W, Testori A, Marsden J, Punt C, Salès F, Gore M, Mackie R, Kusic Z, Dummer R, Patel P, Schadendorf D, Spatz A, Keilholz U, Eggermont A. Adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma: a phase III randomized controlled trial of health-related quality of life and symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol. 2009 Jun 20;27(18):2916-23. doi: 10.1200/JCO.2008.20.2069. Epub 2009 May 11. Erratum in: J Clin Oncol. 2009 Sep 20;27(27):4630. Dosage error in published abstract; MEDLINE/PubMed abstract corrected.
• Fusi A, Collette S, Busse A, Suciu S, Rietz A, Santinami M, Kruit WH, Testori A, Punt CJ, Dalgleish AG, Spatz A, Eggermont AM, Keilholz U. Circulating melanoma cells and distant metastasis-free survival in stage III melanoma patients with or without adjuvant interferon treatment (EORTC 18991 side study). Eur J Cancer. 2009 Dec;45(18):3189-97. doi: 10.1016/j.ejca.2009.09.004. Epub 2009 Sep 28.
• Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, Punt CJ, Salès F, Gore M, Mackie R, Kusic Z, Dummer R, Hauschild A, Musat E, Spatz A, Keilholz U; EORTC Melanoma Group. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. 2008 Jul 12;372(9633):117-26. doi: 10.1016/S0140-6736(08)61033-8.
• Eggermont AM, Suciu S, Santinami M, et al.: EORTC 18991: long-term adjuvant pegylated interferon-alpha2b (PEG-IFN) compared to observation in resected stage III melanoma, final results of a randomized phase III trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-8504, 473s, 2007.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: July 19, 2012): 1258
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Actual Primary Completion Date: August 2003 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed previously resected stage III primary cutaneous melanoma or unknown primary with regional lymph node involvement

  • N1 disease

    • Microscopic, nonpalpable nodal involvement
    • Primary melanoma of any stage with clinically inapparent N1 regional lymph node metastases (T1-4, N1, M0) detected by elective lymph node dissection or sentinel node biopsy

  • N2 disease

    • Palpable nodal involvement with synchronous primary melanoma or apparent nodal disease after prior excision (any pT, N2, M0)
  • Regional lymph node recurrence at any interval after surgery for primary melanoma of any depth (T1-4, rN2, M0)
• Complete resection of primary melanoma with adequate surgical margins
• Full lymphadenectomy must be performed within 70 days of study
• No mucous membrane melanoma or ocular melanoma
• No evidence of distant or nonregional lymph node metastases or in transit metastases (even if previously resected)
• No incompletely resected disease due to gross extracapsular extension

PATIENT CHARACTERISTICS:

Age:

• 18 to 70

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• SGOT and SGPT less than 2 times upper limit of normal
• No active hepatitis

Renal:

• Creatinine less than 2.0 mg/dL

Cardiovascular:

• No severe cardiovascular disease including the following:

  • Arrhythmias requiring chronic treatment
  • Congestive heart failure (New York Heart Association class III or IV)
  • Symptomatic ischemic heart disease

Other:

• No other prior malignancy within the past 5 years except surgically cured nonmelanomatous skin cancer or carcinoma in situ of the cervix
• No thyroid dysfunction unresponsive to therapy
• No uncontrolled diabetes mellitus
• No active autoimmune disease
• No active and/or uncontrolled infection
• No history of neuropsychiatric disorder requiring hospitalization
• No known active alcohol or drug abuse
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior interferon alfa
• No prior immunotherapy for melanoma
• No other concurrent immunologic or biologic therapy
• No concurrent colony stimulating factors including epoetin alfa and filgrastim (G-CSF)

Chemotherapy:

• No prior chemotherapy for melanoma
• No concurrent chemotherapy

Endocrine therapy:

• No prior hormonal therapy for melanoma
• No concurrent hormonal therapy
• No concurrent chronic systemic corticosteroid therapy

Radiotherapy:

• No prior radiotherapy for melanoma
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• Recovered from any prior recent surgery

Other:

• At least 30 days since other prior experimental therapy
• No other concurrent investigational drugs

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Bulgaria, Croatia, Czech Republic, Estonia, France, Germany, Israel, Italy, Netherlands, Poland, Portugal, Slovenia, Spain, Switzerland, Turkey, United Kingdom

Administrative Information

• NCT Number: NCT00006249
• Other Study ID Numbers: EORTC-18991; EORTC-18991
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
• Study Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: Not Provided

Investigators

• Study Chair: Alexander M. M. Eggermont, MD, PhD; Daniel Den Hoed Cancer Center at Erasmus Medical Center

• PRS Account: European Organisation for Research and Treatment of Cancer - EORTC
• Verification Date: February 2015