A Prospective, Multicenter, Study of APF530 (Granisetron) SC for Prevention of CINV in Patients Receiving HEC

Chemotherapy-induced Nausea and Vomiting Clinical Trial

Official title:

A Phase 3 Clinical Study Protocol: A Prospective, Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase 3 Study of APF530 500 mg SC, Fosaprepitant 150 mg IV, and Dexamethasone vs. Ondansetron 0.15 mg/kg IV, Fosaprepitant 150 mg IV, and Dexamethasone for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02106494
• Other study ID #: C2013-01
• Status: Completed
• Phase: Phase 3
• First received: March 28, 2014
• Last updated: July 8, 2016
• Start date: March 2014
• Est. completion date: May 2015

Study information

• Verified date: July 2016
• Source: Heron Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 942
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subjects will be males or nonpregnant females who are 18-75 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chemotherapy-induced Nausea and Vomiting
• Nausea
• Vomiting

Intervention

Drug:
• APF530

• Ondansetron

Locations

Country	Name	City	State
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	The Oncology Institute of Hope and Innovation	Downey	California
United States	North Shore Oncology	East Setauket	New York
United States	Northern Indiana Research	Mishawaka	Indiana
United States	Arizona Oncology Associates, PC-HAL	Pheonix	Arizona
United States	Compassionate Cancer Medical Center	Riverside	California
United States	Northern Indiana Research	South Bend	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Heron Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rate (defined as no emesis and no use of rescue medications) in subjects receiving highly emetogenic chemotherapy.	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 in Cycle 1.	Cycle 1; Day 1 through 5 after adminstration of chemotherapy	No