High-Dose PEG-Intron Pharmacokinetic Study in Patients With Melanoma (Study P04831 AM2)

A Pharmacokinetic Study of PEG-Intron, Administered Weekly in Subjects With High-Risk Melanoma

The purpose of this study is to establish the pharmacokinetics of PEG-Intron, administered at a dose of 6 μg/kg/week for 8 weeks (induction treatment), followed by a dose of 3 μg/kg/week for up to 252 weeks (maintenance treatment), in patients with high risk melanoma.

Inclusion Criteria:

• Subjects at least 18 years of age, of either sex, and of any race.
• Cytologically or histologically-confirmed melanoma, arising from a cutaneous or unknown site of origin, at Stages IIB, IIC, IIIA, IIIB, IIIC according to the American Joint Committee on Cancer (AJCC) 2001 guidelines.
• Adequate hepatic, renal and bone marrow function within 4 weeks prior to initiation of study treatment.
• Subjects presenting with synchronous primary and regional melanoma must have had adequate surgical margins surrounding the primary lesion.
• Full lymphadenectomy must be performed within 90 days prior to initiation of study treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Give informed consent according to International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) and national/local policy.
• Be able to adhere to dose and visit schedules.
• Female subjects of childbearing potential must be using a medically accepted method of birth control prior to Screening and agree to continue its use during the study or be surgically sterilized.
• Female subjects of childbearing potential must have a negative serum pregnancy test at Screening.

Exclusion Criteria:

• Female subjects who are pregnant, intend to become pregnant, or are breastfeeding.

• Previous treatment with interferon alpha, chemotherapy or immunotherapy for melanoma.

• Ocular melanoma, or melanoma of the mucous membranes.

• Evidence of distant or non-regional lymph node metastases.

• In-transit melanoma, even if the lesion has been resected.

• Disease that cannot be completely surgically resected.

• Lack of recovery from recent surgery.

• Prior malignancy within the past 5 years, except surgically cured squamous cell carcinoma of the skin, successfully resected early stage cutaneous melanoma, or cervical carcinoma in situ.

• Severe cardiovascular disease.

• Thyroid dysfunction not responsive to therapy.

• Uncontrolled diabetes mellitus (in the opinion of the investigator).

• Active autoimmune disease.

• Active and/or uncontrolled infection.

• History of seropositivity for human immunodeficiency virus (HIV).

• Pre-existing psychiatric condition.

• Clinical diagnosis of substance abuse of one or more of the following drugs within the following timeframes (excluding time spent in detoxification, hospitalization or incarceration):

  • Alcohol, intravenous drug use, inhalational, psychotropics, narcotics, cocaine, prescription or over-the-counter drugs: within 1 year of the Screening visit.

  • Methadone, buprenorphine hydrochloride (HCl), and/or butorphanol tartrate: within 1 year of Screening visit, unless subject has drug screen negative for other (non-narcotic) drugs documented in the past year and repeated negative within 2 months of Screening visit.

  • Multi-drug abuse (2 or more substances in 16a and 16b): within 3 years of Screening visit.

  • Marijuana:

    • If historic use is deemed excessive by the principal investigator (or medically qualified individual), or is interfering with the subject's life, then the subject is not eligible and should not be screened.
    • If marijuana use is not deemed excessive by principal investigator and does not interfere with life, subject must discontinue any current use of marijuana prior to entry into study.

• Medical condition requiring chronic systemic corticosteroids.

• Known allergy to the drug substance or any of the excipients in the PEG-Intron formulation.

• Any situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study.

• Use of any investigational drugs within 30 days of study entry.

• Participation in other clinical studies of investigational treatments.