Cisplatin, Temozolomide, Abraxane, With Interleukin-2 and Interferon for Metastatic Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 1

Summary: 
      The goal of this clinical research study is to find the highest tolerable dose of Abraxane
      (nab-paclitaxel) when given in combination with cisplatin, Temodar (temozolomide), interferon
      alfa-2b, and interleukin-2 (IL-2) to patients with metastatic melanoma.

      Primary Objective:

        -  The primary objective of the Phase I is to determine the toxicity, safety and the
           maximum tolerated dose maximum tolerated dose of Abraxane in combination with Cisplatin,
           Temozolomide, interleukin-2 and interferon a2b in patients with metastatic melanoma.

      Secondary Objectives:

        -  To assess responses to the combination.

        -  To evaluate the duration of response and the overall survival.

        -  To determine the effectiveness in delaying the appearance of Central Nervous System
           disease.
    

Detailed description: 
      The Study Drugs:

      Cisplatin, nab-paclitaxel, and temozolomide are chemotherapy drugs and have a direct effect
      on melanoma cells. Interferon alfa-2b and IL-2 are biotherapy drugs that stimulate the immune
      system to fight against melanoma. The combination of chemotherapy and biotherapy drugs is
      called biochemotherapy.

      This is the first study using these drugs in combination.

      Catheter:

      If you are found to be eligible to take part in this study, you will have a central venous
      catheter (CVC) inserted, if you do not already have one. The catheter is passed through the
      veins of your arm or the veins that run under your collar bone to reach a wide central vein
      in the chest that runs above your heart. You will receive a separate consent form for this
      procedure, which describes the risks.

      Nab-paclitaxel, cisplatin, and interleukin-2 are given through this catheter. In certain
      situations, blood can also be drawn from this catheter.

      Study Drug Dose Levels:

      You will be assigned to a dose level of nab-paclitaxel based on when you joined this study.
      Up to 3 dose levels of nab-paclitaxel will be tested. Up to 6 participants will be enrolled
      at each dose level. The first group of participants will receive the lowest dose level. Each
      new group will receive a higher dose than the group before it, if no intolerable side effects
      were seen. This will continue until the highest tolerable dose of nab-paclitaxel that can be
      given in combination with the other drugs is found.

      All participants will receive the same dose level of temozolomide, cisplatin, interferon
      alfa-2b, and IL-2.

      Study Drug Administration:

      Each study cycle will last 3-5 weeks. The length of each cycle will depend on your recovery
      from the study drugs.

      On Day 1 of each cycle:

        -  You will take temozolomide by mouth.

        -  You will receive nab-paclitaxel over about 30 minutes by vein about 1 hour after you
           take temozolomide.

        -  You will then receive cisplatin by vein. Each infusion of cisplatin will take about
           45-120 minutes.

        -  You will receive interferon alfa-2b by injection into fatty tissue.

        -  You will begin your IL-2 infusion. The infusion will begin after you receive cisplatin
           and will continue non-stop until Day 5.

      On Day 2 of each cycle:

        -  You will take temozolomide by mouth.

        -  You will receive cisplatin by vein about 1 hour after you take temozolomide.

        -  You will receive interferon alfa-2b by injection into fatty tissue.

      On Day 3 of each cycle:

        -  You will take temozolomide by mouth.

        -  You will receive cisplatin by vein about 1 hour after you take temozolomide.

        -  You will receive interferon alfa-2b by injection into fatty tissue.

        -  Blood (up to 4 teaspoons total) will be drawn for routine tests and tests to check for
           infection in the blood.

      On Day 4 of each cycle:

        -  You will receive cisplatin by vein.

        -  You will receive interferon alfa-2b by injection into fatty tissue.

        -  Blood (up to 4 teaspoons) will be drawn for routine tests.

      On Day 5 of each cycle:

        -  You will receive nab-paclitaxel by vein over about 30 minutes.

        -  You will receive interferon alfa-2b by injection into fatty tissue.

        -  Blood (up to 4 teaspoons) will be drawn for routine tests.

      Depending on how your body reacts to the study drugs, you will stay in the hospital for 7 or
      more days.

      After you are discharged from the hospital, blood (up to 4 teaspoons) will be drawn 2 times a
      week for routine tests.

      Study Visits:

      Before starting each cycle of treatment:

        -  Your medical history will be recorded.

        -  You will have a physical exam.

        -  Blood (about 1-2 tablespoons) will be drawn for routine tests and to check your blood
           counts.

        -  You will have a chest x-ray.

      After every 2 cycles of treatment, you will have CT scans and an MRI scan of the brain to
      check the status of the disease. If you have disease in the bone, you will have a PET/CT to
      check the status of the disease.

      If you have skin lesions, you will have them photographed to check the status of the disease.

      Length of Study:

      You may receive up to 6 cycles of the study drugs. You will be taken off study early if the
      disease gets worse or intolerable side effects occur.

      Follow-Up Contact:

      If you are having follow-up visits with a doctor who is not at M. D. Anderson, you will be
      called 2-4 times a year to learn what treatments you may be receiving and how are you doing.
      You will continue to receive these calls for as long as possible. The phone calls will take
      about 5 minutes.

      This is an investigational study. Nab-paclitaxel is FDA approved and commercially available
      for breast cancer. Temozolomide is FDA approved and commercially available for brain cancer.
      Cisplatin is FDA approved and commercially available for testicular, ovarian, and bladder
      cancers. Interferon is FDA approved and commercially available for patients with melanoma who
      are having surgery. IL-2 is FDA approved and commercially available for melanoma and kidney
      cancer. The combination of these drugs is investigational.

      Up to 24 patients will be take part in this study. All will be enrolled at M. D. Anderson.
    

Intervention name(s): Temozolomide; Abraxane; Cisplatin; Interleukin-2; Interferon alpha 2b
Intervention type(s): Drug; Drug; Drug; Biological; Biological
Intervention description(s): 250 mg/m^2 by mouth on days 1, 2, and 3 of each 21-day cycle.; 100 mg/m^2 given in a short intravenous infusion 1 hour after completion of Temozolomide and a 2nd dose of 70 mg/m^2 given on day 5 of each 21-day cycle.; 20 mg/m^2 intravenously on days 1, 2, 3, and 4 delivered immediately after Abraxane of each 21-day cycle.; 9 MIU/m^2 in a continuous intravenous infusion over 24 hours on days 1, 2, 3, and 4 (total of 96 hours) beginning after completion of Cisplatin of each 21-day cycle.; 5 MIU/m^2 in subcutaneous injection on days 1, 2, 3, 4, and 5 of each 21-day cycle.
Other intervention name(s): Temodar; Nab-paclitaxel; Paclitaxel (protein-bound); ABI-007; Platinol-AQ; Platinol; CDDP; IL-2; Proleukin; Intron A
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Temozolomide; Interleukin-2
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Melanoma; Abraxane; Nab-paclitaxel; Paclitaxel (protein-bound); ABI-007; Cisplatin; Platinol-AQ; Platinol; CDDP; Interleukin 2; IL-2; Proleukin; Intron A; Interferon alpha 2b; Interferon alfa-2b; Temodar; Temozolomide