Study of Patients With Stage IV Malignant Melanoma Using PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Bortezomib; Interferon Alfa-2b
Intervention description: VELCADE (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2 IV based on patient cohort). After three patients have received 5 weeks of therapy (1 cycle) at the initial dose of VELCADE (1.0 mg/m2, Cohort 1) with no dose limiting toxicity, the dose will be raised to 1.3 mg/m2 for the next cohort of three patients. If this dose level is well-tolerated in three consecutive patients, the dose of VELCADE will be raised to 1.6 mg/m2.; I = IFN-α-2b (INTRON A): 5 million units (MU)/m2 SC. INTRON A (5MU/m2) will be administered subcutaneously on Days 1, 3 and 5 of Week 0. During Cycle I, INTRON A will be administered on Days 1, 3 and 5 of Weeks 1-3 of and on Days 1 and 3 of Week 4 to allow for surgical biopsy on Day 5. During Cycles II-V, IFN-α will be administered on Days 1, 3 and 5 of Weeks 1-4. To assess the toxicity profile of IFN-α-2b alone, no VELCADE will be administered during Week 0.
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Bortezomib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: malignant; melanoma

Summary:

      The purpose of this study is to determine the safety, tolerability and dose limiting
      toxicities (DLTs) of VELCADE when administered in combination with interferon-alpha-2b
      (IFN-α-2b) to patients with metastatic malignant melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  must have histological or cytological diagnosis of cutaneous melanoma and clinical
             evidence of metastatic, non-resectable regional lymphatic, or extensive in transit
             recurrent disease. Patients who have had resected metastases will also be eligible
             provided they have measurable disease.

          -  have measurable disease. Measurable disease is defined as the presence of at least one
             measurable lesion.

          -  ECOG performance status ≤ 2 (Karnofsky ≥ 60%).

          -  Female subjects must be either surgically sterilized or willing to use an acceptable
             method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm
             with spermicide, condom with spermicide, or abstinence) for the duration of the study.
             Male subjects must agree to use an acceptable method for contraception for the
             duration of the study.

          -  Patients must have normal organ and marrow function.

          -  Prior Therapy: Patients with an ECOG performance status of ≤ 2 will be eligible for
             this protocol regardless of the number of prior treatments provided they have
             recovered from the reversible effects of prior therapy. Patients are permitted to have
             received therapy with adjuvant IFN-α2b, if it was completed > 6 months prior to
             enrollment in the current study.

          -  Patients with brain metastases are eligible for entry into the study, but must have
             received definitive therapy consisting of external beam radiation therapy, gamma knife
             therapy or surgical resection and be clinically stable. Four weeks after the
             definitive therapy is completed, repeat MRI or CT scans must demonstrate stabilization
             of disease, and there must be no requirement for Decadron. If the patient does not
             have brain metastases, then only one brain CT or MRI is required prior to enrollment
             on study.

        Exclusion Criteria:

          -  Patients meeting any of the following exclusion criteria are not to be enrolled in the
             study.

               -  Patient has a platelet count of < 100 × 109/L within 14 days before enrollment.

               -  Patient has an absolute neutrophil count of < 1.0 x 109/L within 14 days before
                  enrollment.

          -  Patient has a calculated or measured creatinine clearance of < 30 mL/minute within 14
             days before enrollment.

          -  Patient has history of significant brain metastases or other clinically significant
             central nervous system disease.

          -  Patient has ≥Grade 2 peripheral neuropathy within 14 days before enrollment.

          -  Patient has hypersensitivity to bortezomib, boron or mannitol.

          -  Patients with evidence of proteinuria on urinalysis.

          -  Female subject is pregnant or breast-feeding.

          -  Received other investigational drugs with 14 days before enrollment.

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

          -  History of serious psychiatric illness that might be exacerbated by IFN-α-2b.