Evaluate PKs and Efficacy Assessment of Palifermin in Patients With Sarcoma
Condition: Sarcoma; Oral Mucositis
MeSH terms: Sarcoma; Mucositis; Stomatitis
Study type: Interventional
Phase: Phase 2

Summary: 
      Primary:

        1. To evaluate the preliminary efficacy of palifermin in reducing the incidence and
           severity of oral mucositis (OM) in patients with sarcoma receiving multicycle
           chemotherapy.

        2. To evaluate the pharmacokinetics (PK) of palifermin when given pre chemotherapy.

        3. To evaluate the safety profile of palifermin when combined with multicycle chemotherapy.

      Exploratory:

        1. To evaluate the biologic effect of palifermin on oral mucosa.

        2. To investigate potential biomarker development by biochemical analysis in blood cells,
           serum, and plasma.

        3. To investigate the effects of genetic variation in mucositis genes, drug metabolism
           genes, and drug target genes on patient response to the treatment regimen.
    

Detailed description: 
      Palifermin is similar to a protein keratinocyte growth factor (KGF) that is naturally made in
      your body in small amounts. The function of palifermin is to stimulate the growth of specific
      cells that form the tissue lining of your mouth and digestive tract. Damage to these cells
      results in the breakdown of the normal protective barrier that these cells usually provide,
      potentially resulting in infection.

      If you are eligible to take part in this study, you will be randomly assigned (as in the toss
      of a coin) to receive either palifermin or placebo by vein 3 days before each cycle of
      chemotherapy. This will be done for 18 weeks (a total of 12 injections). A placebo is a
      substance that looks like the study drug, but which has no active ingredients. The infusion
      time will last 15-30 seconds. At the beginning of the study, for every 3 patients who are
      enrolled on this study, 2 of the 3 will receive palifermin. Neither you nor the study doctor
      will know which study drug you are assigned to receive.

      Within 1 or 2 days before you receive your first dose of palifermin and between 48 to 72
      hours after you receive your first dose of palifermin, additional non-invasive optical
      imaging procedures may be performed. The purpose of these imaging procedures is to evaluate
      the effects of palifermin on mucosa (mucosal thickness). The types of optical imaging that
      may be done include optical coherence tomography (OCT), fluorescence and reflectance
      spectroscopy, or confocal microscopy. The oral cavity will be inspected and photographed. A
      probe about the size of a pen will be placed on one or two sites of oral buccal mucosa. A
      beam of light will then be directed to the oral tissue and optical signals will be collected
      from each site. This will take about 1 minute for each site. Before using the probe for each
      new participant, it will be disinfected per standard practice.

      You will receive adriamycin with ifosfamide or cisplatin chemotherapy. Adriamycin will be
      given as a continuous infusion through your central venous catheter (CVC) for 3 days.
      Ifosfamide will be given intravenously (intravenously (IV)--through a needle in your vein)
      through your CVC over 3 hours, every day for 4 days. Mesna will be given as a 24-hour IV
      infusion through your CVC every day for 4 days through the same catheter. Mesna is used to
      protect against bladder-related side effects. For patients with certain types of sarcoma,
      vincristine will be given through the catheter by rapid infusion on Day 1 only. In patients
      with bone sarcoma, cisplatin will be given on the first day as IV or intra-arterial infusion
      over around 4 hours instead of ifosfamide.

      You will need to come in to M. D. Anderson every 3 weeks for about 4 to 5 months during the
      treatment period, unless your doctor decides you need to come in more frequently. At these
      visits, you will have your vital signs measured and routine blood tests (about 3 teaspoons
      each) will be performed. In addition, you may have your oral cavity examined and photographed
      before and after receiving the study drug. Every effort will be made to take photographs in
      which you cannot be identified.

      Additional blood samples (about 3 teaspoons) will be taken before each cycle and as
      frequently as needed to measure your blood count and other tests to monitor the drug side
      effects and treatment effects. By the end of the study, you will have given about 10
      tablespoons of blood. This amount includes the optional blood draws should you choose to
      allow it to be drawn.

      You will be responsible for notifying study staff (at your doctors visits or over the phone
      with the study staff) of any side effects you experience or medications (over the counter or
      prescription) that you take during the treatment period. You will also be required to notify
      any other doctors (separate from the study doctors) you see that you are participating in
      this research study.

      If your anemia becomes severe while you are on study, then a transfusion may be recommended.
      If mucositis develops, the prohibited medicines can be allowed for treatment of the
      condition. If you experience an intolerable side effect while on study, you may be taken off
      study. If you leave the study early for any reason, your doctor will continue to follow your
      progress for 4 weeks and will access your medical records for a minimum of 1 year after the
      last dose of study drug (either palifermin or placebo) was given.

      At your end of study visit, you will be evaluated for your disease status with imaging
      studies [computed tomography (CT) scans or magnetic resonance images (MRI)] and your weight
      and vitals signs will be measured. You will report any medications you have taken since your
      last visit and any side effects or blood transfusion that you have had. You will also have a
      final blood draw (about 3 teaspoons) for routine tests.

      The total length of your involvement in this study is expected to be about 18 weeks (4 to 5
      months).
    

Intervention name(s): Palifermin; Placebo; Adriamycin (Doxorubicin); Ifosfamide; Vincristine; Cisplatin
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 180 mcg/kg 3 days prior to chemotherapy; Single dose 3 days prior to chemotherapy; 30 mg/m^2 IV continuous infusion for 72 hours; days 0, 1, 2 (infusion completing on day 3) (total dose = 90 mg/m^2).; 2.5 g/m^2 IV bolus over 3 hours, days 0,1, 2, 3 (total dose = 10 g/m^2); for patients receiving the AI Regimen.; 2 mg IV on day 0, for patients with small cell histology receiving the AI Regimen.; 120 mg/m^2 on day 0, for patients receiving the AP Regimen.
Other intervention name(s): Adriamycin; CDDP; Platinol
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Vincristine; Ifosfamide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Sarcoma; Soft Tissue Sarcoma; Oral Mucositis; Doxorubicin; Adriamycin; Ifosfamide; Palifermin; Vincristine; Cisplatin; Placebo