Fosaprepitant for N/V With High-dose Interleukin-2 for Metastatic Melanoma and Renal Cell Carcinoma
Condition: Chemotherapy-induced Nausea and Vomiting
MeSH terms: Carcinoma; Melanoma; Carcinoma, Renal Cell; Vomiting
Intervention: Fosaprepitant
Intervention description: During treatment admission, intravenous fosaprepitant 150 mg every 48 hours during 6-day hospital admission
Intervention MeSH terms: Fosaprepitant; Aprepitant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: melanoma; renal cell carcinoma; interleukin-2

Summary:

      The purpose of this study is to investigate the effectiveness of intravenous fosaprepitant
      therapy to reduce nausea and vomiting during the treatment of high dose interleukin-2 (HD
      IL-2) therapy for metastatic melanoma or metastatic renal cell carcinoma. Fosaprepitant is an
      intravenous (IV) medication that is FDA- approved for use in adults for the prevention of
      nausea and vomiting during chemotherapy. Fosaprepitant works by blocking the neurokinin-1
      receptor, which is a receptor in the brain that is known to cause nausea and vomiting. Past
      studies estimate that up to 70% of patients undergoing treatment with HD IL-2 will have
      nausea and/or vomiting. While fosaprepitant has been used in clinical practice to treat
      nausea and vomiting during HD IL-2, there have not been any studies done to see how well it
      works. All patients will receive treatment (IV fosaprepitant) during the study during either
      the first or second hospital admission for HD IL-2. On the admission that the subject is not
      receiving IV fosaprepitant, the subject will receive placebo (a medicine that looks like
      fosaprepitant, but is not active). The study is double-blinded, which means neither the
      subject, nor the study doctor will know to which group you have been assigned to that
      admission (IV fosaprepitant or placebo). This study design was chosen to limit the potential
      for bias, which means the trial was designed to try to ensure that unknown factors do not
      affect trial results. When patients start the study, patients will be randomly assigned to
      one of two groups: those who receive treatment (IV fosaprepitant) first and those who receive
      placebo first. During the first admission, subjects will be given the IV fosaprepitant or IV
      placebo during admission. During the second admission, subjects will 'crossover' and receive
      the other treatment that they did not receive during the first admission. Improvement in
      nausea and vomiting will be assessed by counting the number of nausea and vomiting episodes,
      recording if the subject needs additional medication for nausea and vomiting, and by using
      patient questionnaires.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must meet all of the following inclusion criteria to be eligible for
             enrollment into the study:

               1. Evidence of a personally signed and dated informed consent document indicating
                  that the subject (or legally acceptable representative) has been informed of all
                  pertinent aspects of the trial.

               2. Subjects who are willing to comply with scheduled visits, treatment plan,
                  laboratory tests, and other study procedures.

               3. Be at least 18 years of age at the time of informed consent.

               4. Has a diagnosis of metastatic melanoma or metastatic renal cell carcinoma and who
                  will undergo high-dose interleukin-2 (HD IL-2) therapy

               5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
                  at Baseline/Day 1 visit. (See Appendix 6 on p. 51, ECOG Performance Status)

               6. Female of reproductive potential must agree use non-hormonal methods to avoid
                  pregnancy during study participation and for 1 month after last dose of study
                  drug

        Exclusion Criteria:

          -  Subjects presenting with any of the following will not be included in the study:

               1. Women who are pregnant or lactating, or planning pregnancy

               2. Women of childbearing potential who refuse to use non-hormonal methods to avoid
                  pregnancy

               3. Known hypersensitivity to any component of fosaprepitant or aprepitant

               4. Have taken pimozide or cisapride <4 weeks, cytochrome P450 3A4 inducers within 30
                  days, strong CYP3A4 inhibitors within 7 days, or antiemetics within 48 hours
                  prior to treatment initiation (See Appendix 7 on p. 52 for list of CYP3A4
                  inducers and strong CYP3A4 inhibitors)

               5. Have evidence of clinically significant and unstable diseases or conditions such
                  as cardiovascular, immunosuppressive, hematologic, hepatic, neurologic, renal,
                  endocrine, collagen-vascular, or gastrointestinal abnormalities that the
                  investigator thinks may interfere with study participation

               6. Participation in other study using an investigational or experimental therapy or
                  procedure within 4 weeks or 5 half-lives (whichever is longer) before study entry

               7. Subjects cannot participate in studies of other investigational or experimental
                  therapies or procedures at any time during their participation in this study.

               8. Other severe acute or chronic medical or psychiatric condition or laboratory
                  abnormality that may increase the risk associated with study participation or may
                  interfere with the interpretation of study results and, in the judgment of the
                  investigator, would make the subject inappropriate for entry into this study.

               9. Subjects who are investigational site staff members or who are Sponsor employees
                  directly involved in the conduct of the trial.

              10. A subject who, in the opinion of the investigator or sponsor, will be
                  uncooperative or unable to comply with study procedures.