A Prospective, Multicenter, Study of APF530 (Granisetron) SC for Prevention of CINV in Patients Receiving HEC
Condition: Chemotherapy-induced Nausea and Vomiting
MeSH terms: Nausea; Vomiting
Intervention: APF530; Ondansetron; Ondansetron placebo; APF530 placebo; Fosaprepitant; Dexamethasone
Intervention MeSH terms: Dexamethasone; Ondansetron; Fosaprepitant; Aprepitant; Granisetron
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 942.0
Sex: All
Minimum age: 18 Years
Maximum age: 87 Years
Healthy volunteers: No
Keywords: Highly emetogenic chemotherapy (HEC); Chemotherapy-Induced Nausea and Vomiting (CINV)

Summary:

      The primary study objective is to demonstrate the superiority of APF530 500 mg given
      subcutaneously (SC) compared with ondansetron 0.15 mg/kg given intravenously (IV) (up to a
      maximum of 16 mg) in the delayed-phase (> 24-120 hours) complete response (CR) rate (defined
      as no emesis and no use of rescue medications) in subjects receiving highly emetogenic
      chemotherapy (HEC) as defined by the 2011 ASCO CINV guidelines
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects will be males or nonpregnant females who are 18-87 years of age at the time
             of enrollment.

          -  Subjects must have histologically or cytologically confirmed malignant disease.

          -  Subjects must be undergoing treatment with a HEC regimen according to the 2011 ASCO
             CINV guidelines for further details on the emetogenic classifications of chemotherapy
             agents for this study).

          -  A life expectancy > 6 months

          -  Subjects must be able to receive standardized doses of dexamethasone as required in
             the protocol for the prevention of emesis.

          -  Subjects must be characterized as having Eastern Cooperative Oncology Group (ECOG)
             performance status of 0 or 1.

          -  Subjects must have adequate bone marrow, kidney, and liver function.

          -  Subjects must be able to swallow oral medications (pills) without difficulty.

          -  Subjects must be entering the first cycle of their current chemotherapy regimen.

          -  Subjects must be willing and able to comply with all testing and requirements defined
             in the protocol.

          -  Subjects must be able to provide voluntary, written, informed consent to participate
             in this study and must be able to fully understand the study requirements.

          -  Female subjects cannot be pregnant and must be adequately protected from conception
             for the duration of study, using at least one form of contraception. It is recommended
             that females and female partners of male subjects remain adequately protected from
             conception during the study and for up to 1 year following study participation.

        Exclusion Criteria:

          -  Subject has a known hypersensitivity to granisetron or any 5-HT3 receptor antagonist.

          -  Subject has a history or presence of clinically significant abnormal 12-lead ECG or an
             ECG with QTc by Bazett's correction of > 450 msec in men and > 470 msec in women on
             the screening ECG.

          -  Subject has PR > 240 msec, QRS > 110 msec, or a history of prolongation of QT
             interval.

          -  Subject has a family history of long QT syndrome.

          -  Subject has a history of cardiac disease, including congenital long QT syndrome,
             angina, myocardial ischemia or infarction, congestive heart failure, myocarditis, or
             chest pain or dyspnea on exertion.

          -  Subject has an electrolyte disturbance, such as uncorrected hypokalemia/hyperkalemia,
             hypomagnesemia, or hypocalcemia.

          -  Subject has idiopathic cardiomyopathy, syncope, epilepsy, hypertrophic cardiomyopathy,
             or other clinically significant cardiac disease.

          -  Subject is pregnant or breast-feeding.

          -  Subject is planning to receive multiple-day chemotherapy.

          -  Subject has taken any of the following agents within 7 days prior to initiation of
             chemotherapy (the study): 5-HT3 receptor antagonists, phenothiazines, benzamides,
             domperidone, cannabinoids, or NK-1 receptor antagonist.

          -  Subject has taken any benzodiazepine within 1 day (24 hours) prior to initiation of
             chemotherapy (the study).

          -  Subject is scheduled to receive any other chemotherapeutic agent from Day 2 through
             Day 6.

          -  Subject is scheduled to receive any radiation therapy to the abdomen or pelvis from
             Day -5 through Day 6.

          -  Subject has received systemic corticosteroids or sedative antihistamines within 72
             hours of Day 1 of the study, except as premedication for chemotherapy (e.g., taxanes,
             pemetrexed).

          -  Subject has symptomatic primary or metastatic central nervous system (CNS) disease.

          -  Subject has ongoing vomiting, retching, or nausea caused by any etiology, or has a
             history of anticipatory nausea and vomiting.

          -  Subject has vomited and/or has had dry heaves or retching within 24 hours prior to the
             start of HEC on Day 1.

          -  Subject is NOT able to swallow oral medications (pills) without difficulty.