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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Chemotherapy-Induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Intranasal granisetron


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5 mg of TRG (intranasal granisetron)<br>0.5 mg dose, intranasal powder, single spray, administered once | Drug: Intranasal granisetron<br>* 0.5 mg, 1.0 mg or 2.0 mg dose of TRG prior to the administration of a highly-emetogenic chemotherapy regimen<br>* Other names: TRG;|
| Experimental: 1.0 mg of TRG (intranasal granisetron)<br>1.0 mg dose, intranasal powder, songle spray, administered once | Drug: Intranasal granisetron<br>* 0.5 mg, 1.0 mg or 2.0 mg dose of TRG prior to the administration of a highly-emetogenic chemotherapy regimen<br>* Other names: TRG;|
| Experimental: 2.0 mg of TRG (intranasal granisetron)<br>2.0 mg dose, intranasal powder, single spray, administered once | Drug: Intranasal granisetron<br>* 0.5 mg, 1.0 mg or 2.0 mg dose of TRG prior to the administration of a highly-emetogenic chemotherapy regimen<br>* Other names: TRG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Complete Control | Complete Control is defined as no emetic episodes, no use of rescue medications, and no more than mild nausea as defined by a categorial scale. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Complete Response | Complete Response is defined as no emetic episodes and no use of rescue medications | 24 hours | 
| Percentage of Patients With Total Response | Total Response is defined as no nausea, no emetic episodes, and no use of rescue medications | 24 hours | 
| Percentage of Patients With Major Control of Emesis | Major Control of emesis = 2 emetic episodes | 24 hrs | 
| Percentage of Patients With Minor Control of Emesis | Minor Control of emesis: 3-5 emetic episodes | 24 hrs | 
| Percentage of Patients With Failure | Failure: > 5 emetic episodes | 24 hrs | 
| Percentage of Patients Using Rescue Medications |  | 24 hours | 
| Time to First Emetic Episode |  | 24 hours | 
| Time to First Rescue Medication |  | 24 hours | 
| Time to Treatment Failure | Time to treatment failure is based on time to first emetic episode or time to rescue medication, whichever occurs first | 24 hours | 
| Number of Emetic Episodes |  | 24 hours | 
| Severity of Nausea Measured by a 4 Categorical Scale | 4 categorical scale: none, mild (did not interfere with normal daily life), moderate (interfered with normal daily life), and severe (bedridden due to nausea/ required the patient to be bedridden) | 24 hours | 
| Patient Global Satisfaction With Antiemetic Therapy Measured by a VAS | VAS (visual analog scale) 0: not at all satisfied, 100: totally satisfied | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Highly emetogenic chemotherapy induced nausea and vomiting