Efficacy and Safety of High-dose Interferon Alfa-2b (Intron A®) for the Adjuvant Treatment of Malignant Melanoma (Study P04083)

Efficacy and Safety of High-dose Treatment With the Immunomodulator Interferon-α-2b (Intron A®) for the Adjuvant Treatment of Malignant Melanoma.

The aim of this observational study is to document the efficacy and tolerability of high-dose interferon therapy in adult participants with malignant melanoma at high risk of relapse and to compare them with the survival times and relapse rates in previous studies (historical control).

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: Interferon α-2b

Detailed Description

Observational study to evaluate the tolerability and efficacy (vs historical controls) of a high-dose therapy scheme with interferon-α-2b (IntronA®):

Adjuvant treatment with interferon-α-2 has been demonstrated in a number of studies to have an antiproliferative effect on malignant melanoma. In these cases a response rate of up to 20% could be achieved with a dose of 10 million IU or more 3x/week or daily. Kirkwood et al. showed in a study carried out in ECOG (the Eastern Cooperative Oncology Group, study no. 1684) that there was a clear and significant survival advantage versus the observation group with the following dose:

20 mio IU/m² interferon-α-2b (IntronA®) 5x/week iv over the course of one month followed by 11 months with 10 mio IU/m² 3x/week sc.

• Study Type: Observational
• Enrollment (Actual): 138

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult participants in Austria with malignant melanoma at high risk of relapse

Description

Inclusion Criteria:

• Male and female participants
• Age 18-70 years
• Malignant melanoma stage II or III (>/= 1.5 mm tumor thickness, no distant metastases or Malignant melanoma with lymph node metastases or Lymph node metastases with unknown primary tumor
• An excision border of at least 2 cm around the primary tumor
• Therapy must start within 12 weeks after surgery of the tumor/of the lymph node metastases
• ECOG status 0-1 (= Karnofsky Index >/= 80)

• Laboratory parameters

  • Hematocrit >= 33%
  • Leukocytes >= 3000/μl
  • Thrombocytes >= 100000/μl
  • Alanine aminotransferase(ALT) <= 2x normal values
  • Bilirubin <= 2x normal values

Exclusion Criteria:

• Known allergy to one of the medications or any of its component parts
• Refusal on the part of participants capable of childbearing to use a reliable contraceptive
• Lactating mothers
• Presence of distant metastases
• Another primary tumor of different histological origin than corresponding to the indication (except when the relapse-free interval is > 5 years, or the tumor is a cervical carcinoma in situ, a basal cell carcinoma or cutaneous squamous cell carcinoma)
• Participants on corticosteroid treatment or treatment with an immunomodulating substance
• Preexisting psychiatric illness, particularly serious depression
• Prior adjuvant radio-, chemo-, or immuno-therapy
• Treatment with an investigational drug within the prior 30 days
• Participant history that includes cardiac arrhythmia, cardiac insufficiency requiring treatment, or anthracycline administration
• Myocardial infarction within the prior year
• An unstable medical condition (apart from the indication) that in the judgment of the investigating physician excludes the participants from the study
• Psoriasis (a relative exclusion criterion, since interferon can aggravate psoriasis; decision to be based on risk/benefit analysis)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adults with malignant melanoma at high risk of relapse; Adults with malignant melanoma of the following stages: II and III (>/= 1.5 mm Breslow thickness without distant metastases; melanoma with lymph node metastases	Biological: Interferon α-2b; 20 mio IU/m² interferon-α-2b 5x/week intravenously (IV) over the course of 1 month, followed by 10 mio IU/m² interferon-α-2b 3x/week subcutaneously (SC) for 11 months.; Other Names: Intron A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Disease Recurrence	Number of participants with disease recurrence was being measured.	Throughout 12 months of treatment and 24 months of follow-up
Relapse Free Survival Time	Median time to recurrence according to Kaplan Maier evaluation	Throughout 12 months of treatment and 24 months of follow-up

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: December 1, 1996
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: September 8, 2008
• First Submitted That Met QC Criteria: September 8, 2008
• First Posted (Estimate): September 9, 2008

Study Record Updates

• Last Update Posted (Estimate): October 19, 2015
• Last Update Submitted That Met QC Criteria: October 16, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: interferon-alpha
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons
• Other Study ID Numbers: P04083