Fosaprepitant in Patients Receiving Ifosfamide-based Regimen
Condition: Sarcoma; Chemotherapy-induced Nausea and Vomiting; Effects of Chemotherapy; Adverse Effects of Medical Drugs
MeSH terms: Sarcoma; Nausea; Vomiting
Study type: Interventional

Summary: 
      The goal of this clinical research study is to learn how different doses of fosaprepitant may
      effect how ifosfamide-based chemotherapy is absorbed by the body. Researchers also want to
      learn if fosaprepitant can help to control or prevent delayed nausea and/or vomiting that may
      be caused by chemotherapy. The safety of this drug will also be studied.

      Fosaprepitant is designed to block the natural substance in the brain that causes nausea and
      vomiting. This may help to prevent and/or control nausea and vomiting caused by chemotherapy.
    

Detailed description: 
      Study Groups:

      If you are found to be eligible to take part in this study, you will receive fosaprepitant
      during 21-day chemotherapy cycles. You will be randomly assigned (as in a toss of dice) to 1
      of 2 study groups, each with 2 divisions:

        -  If you are in Group A1, you will receive fosaprepitant on Day 1 of Cycle 1.

        -  If you are in Group A2, you will receive fosaprepitant on Day 1 of Cycle 2.

        -  If you are in Group B1, you will receive fosaprepitant on Days 1 and 4 of Cycle 1.

        -  If you are in Group B2, you will receive fosaprepitant on Days 1 and 4 Cycle 2.

      You and the study staff will know to which group and division you are assigned. Each time you
      receive the drug, you will receive it by vein over about 20-30 minutes.

      You will also receive the ifosfamide-based chemotherapy prescribed by your doctor, as well as
      standard drugs for preventing nausea and vomiting (such as ondansetron, lorazepam,
      diphenhydramine, and promethazine). You will sign a separate consent form that will describe
      these treatments in detail, along with their risks.

      You will receive dexamethasone before chemotherapy, every day for 5 days, to help prevent
      nausea and vomiting.

      Before each chemotherapy cycle, you will be given a study diary. Each day, you will record
      any side effects you may . You should bring your study diary to every study visit so the
      study staff can review it.

      Study Visits:

      Before each cycle that you receive fosaprepitant, the following tests and procedures will be
      performed:

        -  You will have a physical exam.

        -  Your vital signs, weight, and performance status will be recorded.

        -  You will fill out the same questionnaire you did at screening.

        -  You will be asked about any other drugs you may be taking. Be sure to tell the study
           doctor about all drugs (including vitamins, herbal products, and nutritional
           supplements), because some drugs/substances will cause side effects when taken at the
           same time as fosaprepitant.

        -  Blood (about 5 teaspoons) will be drawn for routine tests.

      Blood (about 1 teaspoon) will also be drawn 2 times each week during Cycles 1 and 2 for
      routine tests.

      Pharmacokinetic Testing:

      On Days 1 and 4 of Cycles 1 and 2 of chemotherapy, blood samples (about 2 teaspoons each
      time) will be drawn for pharmacokinetic (PK) testing, when possible. PK testing measures the
      amount of study drug in the body at different time points. The blood will be drawn before you
      receive ifosfamide, at the end of the infusion, and 4 more times in the 24 hours after the
      infusion.

      Length of Study:

      You may receive up to 6 cycles of chemotherapy (and up to 5 cycles of fosaprepitant). You
      will no longer be able to take the study drug if the disease gets worse or if intolerable
      side effects occur.

      Your participation on the study will be over once you have completed the end-of-study visit.

      End-of-Study Visit:

      About 3 weeks after your last dose of fosaprepitant, you will return for an end-of-study
      visit. At this visit, the following tests and procedures will be performed:

        -  You will have a physical exam.

        -  Your vital signs, weight, and performance status will be recorded.

        -  You will fill out the same questionnaire you did at screening.

        -  You will be asked about any other drugs you may be taking.

        -  Blood (about 5 teaspoons) will be drawn for routine tests.

      This is an investigational study. Fosaprepitant is FDA approved and commercially available in
      combination with other drugs for the prevention of nausea and vomiting that may be caused by
      chemotherapy. It is investigational to study how fosaprepitant may affect the drug levels of
      ifosfamide in the blood and how many doses should be given.

      Up to 36 patients will take part in this study. All will be enrolled at MD Anderson.
    

Intervention name(s): Fosaprepitant; Dexamethasone; 5HT3 receptor antagonist; Ifosfamide-based chemotherapy (AI); Doxorubicin; Mesna; Ifosfamide; Vincristine
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 150 mg administered intravenously, delivered in either single dose or two doses, on Day 1 for single dose and on Days 1 and 4 for two doses, varying between Cycle 1 or Cycle 2 depending upon randomization to arm.; Intravenous push (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5); 5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy; Doxorubicin + Mesna + + Ifosfamide + Vincristine, chemotherapy cycles repeated every 3-4 weeks for up to 6 cycles. Chemotherapy drugs listed separately, individual dosages, etc.; 25 mg/m^2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m^2) as part of AI Chemotherapy.; Prior to ifosfamide (Day 1) - 500 mg/m^2 (20% of ifosfamide dose) given simultaneously with ifosfamide and then daily continuous infusion (Days 1-4 completing infusion on day 4) - 1,500 mg/m^2/day (60% of daily ifosfamide dose) for a total of 6 gm/m^2. The mesna infusion complete 24 hours after last dose of ifosfamide.; 2.5 g/m^2 IV bolus over 3 hours on days 1, 2, 3, 4 (total dose: 10 g/m^2).; 2 mg IV by rapid infusion (Day 1) may be given to participants with sarcomas of small cell histology.
Other intervention name(s): Fosaprepitant Dimeglumine; Dexamethasone acetate; Decadron; Rubex; Adriamycin; Adriamycin RDF; Adriamycin PFS; Doxorubicin Hydrochloride; Mesnex; Ifex
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Doxorubicin; Liposomal doxorubicin; Vincristine; Ifosfamide; Isophosphamide mustard; Fosaprepitant; Aprepitant; BB 1101
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: cancer; fosaprepitant; Ifosfamide-based Multi-day Chemotherapy; Chemotherapy-induced nausea and vomiting; CINV; multi-day chemotherapy regimens; antiemetics; adverse effect; doxorubicin plus ifosfamide; AI; AI and vincristine; VAI; aprepitant; prevention; nausea; vomiting; emetogenic chemotherapy