Phase 2 Study of Efficacy, Tolerability, and Safety of Intranasal Granisetron for Chemo-Induced Nausea and Vomiting

A Randomized, Single Administration, Double-blind, Parallel-group Phase 2 Dose Finding Study to Assess the Efficacy, Tolerability, and Safety of TRG (Intranasal Granisetron) in Patients With Chemotherapy-induced Nausea and Vomiting (CINV) Associated With the Administration of Highly Emetogenic Chemotherapy

Brief Summary: A randomized, single administration, double-blind, parallel- group Phase 2 dose finding study to assess the efficacy, tolerability, and safety of TRG in patients with chemotherapy-induced nausea and vomiting (CINV) associated with the administration of highly emetogenic chemotherapy.

Primary Objective: To select a dose for Phase 3 by assessing the efficacy, safety, and tolerability of 3 doses of TRG in patients with CINV associated with the administration of highly emetogenic chemotherapy.

Inclusion Criteria:

• Patients with histologically and/or cytologically confirmed cancer
• ECOG performance status of 0, 1, or 2
• Patients with life expectancy of at least 3 months
• Patients who are chemotherapy naïve
• Patients who will be receiving the first cycle of a highly emetogenic regimen according to the MASCC criteria or the Hesketh criteria
• Patients with adequate metabolic or hematologic values for chemotherapy
• Patients with intact nasal mucosa
• Non child-bearing potential patients
• Patients able to read and write at a competent level, and capable of giving legal consent
• Patients who have provided written informed consent

Exclusion Criteria:

• Patients who do not receive a chemotherapy regimen which is a highly emetogenic chemotherapy regimen according to the MASCC or the Hesketh criteria
• Patients with nasal cancers, pharyngeal cancers, maxillary sinus cancers, or ethmoid sinus cancers
• Patients with nasal ulcers, septal perforation, or other nasal conditions that may interfere with IN administration
• Patients with any episode of retching, vomiting, or uncontrolled nausea within 48 hours before dosing with TRG and/or administration of chemotherapy
• Patients who have received radiation therapy in the 14 days before dosing with TRG, or for whom radiation therapy is scheduled during the 7 days after a TRG dose
• Patients who have received any investigational product within 30 days prior to study entry
• Patients who have received any drug or who were scheduled to receive any drug with antiemetic efficacy within 24 hours of the start of treatment
• Patients who have an allergy or hypersensitivity to granisetron or other selective 5hydroxytryptamine3(5-HT3) receptor antagonists
• Patients with ECOG performance status of 3 or 4
• Patients who have or have a history of brain tumors, head cancers, or neck cancers
• Patients who have a psychological problem that, in the Investigator's opinion, is severe enough to interfere with study eligibility or with interpretation of study results
• Patients who are pregnant (urine test) or breastfeeding
• Patients who have received prior cytotoxic chemotherapy given for the treatment of cancer
• Patients scheduled to receive multiple day chemotherapy
• Patients with clinically relevant abnormal laboratory values at the discretion of the Investigator
• Patients with clinically relevant hepatic, renal, infectious, neurological, or psychiatric disorders, or any other major systemic illness at the discretion of the Investigator
• Patients with any prevalence or cause of nausea and vomiting other than chemotherapy
• Patients using systemic steroids for any indication, or patients using steroids other than dexamethasone for prevention of chemotherapy-induced nausea and vomiting, or patients using dexamethasone for chemotherapy-induced nausea and vomiting at doses other than recommended in the MASCC antiemetic guidelines
• Patients with a QT interval greater than 500 ms or with acute ischemic changes or cardiac abnormality predisposing to arrhythmia on screening electrocardiogram (ECG) or by history
• Patients with a history of drug and/or alcohol abuse.