Dose-finding Study of APD403 to Prevent Nausea and Vomiting After Chemotherapy
Condition: CINV
MeSH terms: Vomiting
Intervention: Ondansetron; Placebo; Dexamethasone; Fosaprepitant; APD403 IV; APD403 oral
Intervention description: 5HT3-antagonist; Comparator; Corticosteroid; NK1 antagonist; Amisulpride IV 20 mg; Amisulpride oral 10, 20 or 40 mg
Intervention MeSH terms: Dexamethasone; Ondansetron; Fosaprepitant; Aprepitant
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 342.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Comparison of efficacy of APD403 at preventing delayed sickness in patients who have received
      cancer chemotherapy
    

Eligibility criteria:

        Inclusion criteria

          -  Male or female patients ≥ 18 years of age

          -  Ability and willingness to give written informed consent

          -  Patients scheduled to receive, on day 1 of their chemotherapy, either: (i) a first
             cisplatin chemotherapy infusion at a dose of ≥70 mg/m2 (males and females); or (ii) a
             first infusion of cyclophosphamide at a dose of 500-1500 mg/m2 in combination with
             either epirubicin at a dose of 60-100 mg/m2 or doxorubicin at a dose of 40-60 mg/m2
             (females only)

          -  Karnofsky performance score ≥ 60%

          -  Adequate cardiac, hepatic and renal function

               -  QTc interval < 500 ms

               -  Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 5 x
                  upper limit normal (ULN)

               -  Bilirubin < 5 x ULN

               -  Creatinine < 3 x ULN

          -  Adequate haematological function

               -  Haemoglobin ≥ 8 g/dL

               -  White blood count ≥ 3.0 x 109/L

               -  Platelet count ≥ 100 x 109/L

          -  For females of child-bearing potential: ability and willingness to use a highly
             effective form of contraception (e.g., abstinence from sexual intercourse, surgical
             sterilisation (of subject or partner) or a double-barrier method of contraception such
             as either an intra-uterine device (IUD) or an occlusive cap with spermicide, in
             conjunction with partner's use of a condom) during the study and for a period of at
             least 48 hours afterwards

        Exclusion Criteria

          -  Patients scheduled to receive, prior to or in the 120 hours after cisplatin or AC, any
             other chemotherapeutic agent with a high or moderate emetic risk

          -  Patients who have previously received anti-neoplastic chemotherapy

          -  Patients scheduled to receive paclitaxel or docetaxel during the first cycle of their
             chemotherapy

          -  Patients undergoing abdominal or pelvic irradiation within 48 hours prior to screening
             or scheduled to receive abdominal or pelvic irradiation between screening and 24 hours
             after cisplatin or AC administration

          -  Patients with a known prolactin-dependent tumour (e.g. pituitary gland prolactinoma or
             confirmed prolactin-dependent breast cancer) or phaeochromocytoma

          -  Patients with a pre-existing vestibular disorder

          -  Patients being treated with regular anti-emetic therapy including corticosteroids

          -  Patients receiving inhaled corticosteroids, unless started more than one month prior
             to the expected date of study entry