Study of Denileukin Diftitox in Participants With Stage IIIC and Stage IV Melanoma
Condition: Stage IIIC Melanoma; Stage IV Melanoma
MeSH terms: Melanoma
Intervention: Denileukin diftitox
Intervention description: Denileukin diftitox intravenous infusion over 30-60 minutes.
Intervention MeSH terms: Denileukin diftitox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neoplasms

Summary:

      The purpose of this study is to determine whether participants with Stage IIIC and Stage IV
      Melanoma experience benefit when treated with Denileukin diftitox in two different dosing
      schedules.
    

Eligibility criteria:

        Inclusion Criteria Participants may be entered in the study only if they meet all of the
        following criteria.

          1. Male or female participants greater than or equal to18 years of age;

          2. Participants with histologically confirmed melanoma (Stage IIIC or Stage IV, American
             Joint Commission on Cancer);

          3. Naive to prior systemic chemotherapy, targeted therapy (eg, BRAF), or immunotherapy
             (eg, interleukin-2 [IL-2] or interferon) for the treatment of melanoma, including any
             cytotoxic agents or IL-2 used for adjuvant therapy (adjuvant interferon is allowed).
             Prior granulocyte macrophage colony-stimulating factor (GM-CSF) is allowed;

          4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2;

          5. Life expectancy greater than or equal to 3 months;

          6. At least 1 site of radiographically measurable disease by immune-related response
             criteria (irRC);

          7. Serum albumin greater than or equal to 3 g/dL;

          8. Adequate hematologic, renal, and liver function as defined by laboratory values
             performed within 21 days prior to initiation of dosing:

               -  Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L;

               -  Platelet count greater than or equal to 100 x 10^9/L;

               -  Hemoglobin greater than or equal to 9 g/dL;

               -  Serum creatinine less than or equal 1.5 x upper limit of normal (ULN) or
                  creatinine clearance greater than or equal to 50 mL/min;

               -  Total serum bilirubin less than or equal to 1.5 x ULN;

               -  Serum aspartate transaminase (AST/SGOT) or serum alanine transaminase (ALT/SGPT)
                  less than or equal to 2.5 x ULN, and less than or equal to 5 x ULN if liver
                  metastases are present.

          9. Fertile males should use an effective method of contraception during treatment and for
             at least 3 months after completion of treatment, as directed by their physician;

         10. Pre-menopausal females and females less than 2 years after the onset of menopause
             should have a negative pregnancy test at Screening. Pre-menopausal females must agree
             to use an acceptable method of birth control from the time of the negative pregnancy
             test up to 90 days after the last dose of study drug. Females of non-childbearing
             potential may be included if they are either surgically sterile or have been
             postmenopausal for greater than or equal to 1 year; Before study entry, written
             informed consent must be obtained from the participants prior to performing any
             study-related procedures.

        Exclusion Criteria

        Participants will not be entered in the study for any of the following:

          1. Known central nervous system (CNS) lesions, except for asymptomatic non-progressing,
             treated brain metastases.

             Treated brain metastases are defined as having no evidence of progression or
             hemorrhage for 2 months, as ascertained by clinical examination and brain imaging
             (magnetic resonance imaging [MRI] or computerized tomography [CT]) during the
             Screening period (using the pretreatment brain image as Baseline). Treatment for brain
             metastases must have been completed at least 2 months prior to Day 1 of the first
             treatment cycle and may include whole brain radiotherapy, radiosurgery (Gamma Knife,
             LINAC, or equivalent), or a combination as deemed appropriate by the treating
             physician. Dexamethasone must be discontinued at least 4 weeks prior to Day 1.
             Participants with CNS metastases treated by neurosurgical resection or brain biopsy
             performed within 2 months prior to Day 1 will be excluded;

          2. Carcinomatous meningitis;

          3. Prior treatment with denileukin diftitox;

          4. Known hypersensitivity to denileukin diftitox or any of its components: diphtheria
             toxin, IL-2, or excipients;

          5. Prior surgery for melanoma less than 4 weeks before enrollment;

          6. Other malignancy within 3 years of randomization, with the exception of adequately
             treated carcinoma in situ of the cervix or non-melanoma skin cancer, with no
             subsequent evidence of recurrence and/or malignancies diagnosed at a stage where
             definitive therapy results in near certain cures. The Medical Monitor must be
             consulted in such cases;

          7. Currently receiving any other anticancer treatment for melanoma (including palliative
             radiotherapy);

          8. Received treatment in another clinical study within the 4 weeks prior to commencing
             study treatment or participants who have not recovered from side effects of an
             investigational drug to Common Terminology Criteria for Adverse Events (CTCAE) Grade
             less than or equal to 1, except for alopecia;

          9. Received radiotherapy for non-CNS disease within the 2 weeks prior to commencing study
             treatment or have not recovered from side effects of all radiation-related toxicities
             to Grade less than or equal to 1, except for alopecia;

         10. Significant cardiovascular impairment (history of congestive heart failure New York
             Heart Association [NYHA] Grade greater than 2 [see Appendix 5], unstable angina, or
             myocardial infarction within the past 6 months, or serious cardiac arrhythmia);

         11. Use of chronic systemic steroids (>5 days) within 2 weeks of Day 1 of the first
             treatment cycle (replacement therapy for adrenal insufficiency is allowed);

         12. Participants with an allograft requiring immunosuppression;

         13. Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen,
             or hepatitis C positive;

         14. Pregnant, breast-feeding, or refusing double barrier contraception, oral
             contraceptives, or avoidance of pregnancy measures; Have any other uncontrolled
             infection or medical condition that could interfere with the conduct of the study.