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

Conditions

Chemotherapy-induced Nausea and Vomiting

Keywords

Highly emetogenic chemotherapy (HEC), Chemotherapy-Induced Nausea and Vomiting (CINV)

Brief 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

Ian D. Schnadig, Eduardo Braun, Michael Mosier, Robert B. Geller, Lee S. Schwartzberg

Journal of Clinical Oncology2016-05-203 citations

10.1200/jco.2016.34.15_suppl.e21666

Phase III MAGIC trial of APF530 v ondansetron (Ond) with fosaprepitant (Fos) + dexamethasone (Dex) for highly emetogenic chemotherapy (HEC)-induced nausea and vomiting: analysis by age and gender.

Lee S. Schwartzberg, Nashat Gabrail, John Hrom, Nicholas J. Vogelzang, Michael Mosier et al. (7 authors)

Journal of Clinical Oncology2016-05-201 citations

10.1200/jco.2016.34.15_suppl.e21700

APF530 (Granisetron Injection Extended-Release) in a Three-Drug Regimen for Delayed CINV in Highly Emetogenic Chemotherapy

Ian D. Schnadig, Richy Agajanian, Christopher Dakhil, Nashat Gabrail, Robert E. Smith et al. (13 authors)

Future Oncology2016-03-2122 citations

10.2217/fon-2016-0070

Abstract P1-10-07: Phase 3 comparison of APF530 versus ondansetron, each in a guideline-recommended 3-drug regimen for prevention of chemotherapy-induced nausea and vomiting due to anthracycline + cyclophosphamide (AC)–based highly emetogenic chemotherapy (HEC) regimens: A post hoc subgroup analysis of the MAGIC trial

Ian D. Schnadig, Richy Agajanian, Shaker R. Dakhil, Carolyn Taylor, S Wilks et al. (10 authors)

Cancer Research2016-02-152 citations

10.1158/1538-7445.sabcs15-p1-10-07

Phase III study of APF530 versus ondansetron with a neurokinin 1 antagonist + corticosteroid in preventing highly emetogenic chemotherapy-induced nausea and vomiting: MAGIC trial.

Ian D. Schnadig, Richy Agajanian, Shaker R. Dakhil, Nashat Gabrail, Robert E. Smith et al. (12 authors)

Journal of Clinical Oncology2015-10-01

10.1200/jco.2015.33.28_suppl.68

Interventions

DRUGAPF530

DRUGOndansetron

DRUGOndansetron placebo

DRUGAPF530 placebo

DRUGFosaprepitant

DRUGDexamethasone

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 87 Years

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
Delayed Phase Complete Response (CR) Rate	24 - 120 Hours	Percentage of Participants with no emesis and no rescue medication in patients receiving HEC in the delayed phase (24 to 120 hours) of CINV.

Secondary

Measure	Time frame	Description
Overall Complete Response Rate	0 - 120 Hours	To determine the effect of APF530 on complete response rates in the overall phase (0 to 120 hours) of CINV.
Delayed Complete Control (CC) Rate	24 - 120 Hours	To determine the effect of APF530 on complete control rates defined as no more than mild nausea, no emetic episodes \[vomiting or retching\], and no use of rescue medications in the delayed phase (24 to 120 hours) of CINV.
Overall Complete Control Rate	0 - 120 Hours	To determine the effect of APF530 on complete control rates defined as no more than mild nausea, no emetic episodes \[vomiting or retching\], and no use of rescue medications in the overall phase (0 to 120 hours) of CINV.
Rate of No Emetic Episodes	0 - 120 Hours	To determine the effect of APF530 on the rate of no emetic episodes (vomiting or retching) in the overall phase (0 to 120 hours) of CINV.

Countries

United States

Contacts

STUDY_DIRECTORMark Gelder, MD

Heron Therapeutics

Participant flow

Pre-assignment details

Patients receiving highly emetogenic chemotherapy were stratified by cisplatin and randomized 1:1 to one of two treatment arms

Participants by arm

Arm	Count
APF530 + Fosaprepitant + Dexamethasone Day 1 - Single SC dose of APF530 500 mg (10 mg granisetron) + Placebo for ondansetron IV + Fosaprepitant 150 mg IV + Dexamethasone 12 mg IV Day 2 - Dexamethasone 8 mg PO QD Days 3 and 4 - Dexamethasone 8 mg PO BID	450
Ondansetron + Fosaprepitant + Dexamethasone Day 1 - Single IV dose of Ondansetron 0.15 mg/kg (up to a maximum of 16 mg) + Placebo for APF530 SC + Fosaprepitant 150 mg IV + Dexamethasone 12 mg IV Day 2 - Dexamethasone 8 mg PO QD Days 3 and 4 - Dexamethasone 8 mg PO BID	452
Total	902

Baseline characteristics

Characteristic	APF530 + Fosaprepitant + Dexamethasone	Total	Ondansetron + Fosaprepitant + Dexamethasone
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	117 Participants	235 Participants	118 Participants
Age, Categorical Between 18 and 65 years	333 Participants	667 Participants	334 Participants
Age, Continuous	55.7 years STANDARD_DEVIATION 11.74	55.65 years STANDARD_DEVIATION 11.84	55.6 years STANDARD_DEVIATION 11.94
Sex: Female, Male Female	358 Participants	731 Participants	373 Participants
Sex: Female, Male Male	92 Participants	171 Participants	79 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
other Total, other adverse events	411 / 456	407 / 459
serious Total, serious adverse events	42 / 456	28 / 459

Outcome results

Primary

Delayed Phase Complete Response (CR) Rate

Percentage of Participants with no emesis and no rescue medication in patients receiving HEC in the delayed phase (24 to 120 hours) of CINV.

Time frame: 24 - 120 Hours