Efficacy and Safety of Fosaprepitant Dimeglumine in Preventing Chemotherapy-Induced Nausea and Vomiting (MK-0517-031)

NCT01594749 | Completed Phase 3 Results

• 1 other identifier: 0517-031
• Study Type: interventional
• Target: 1,015
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to demonstrate that, when given concomitantly with a 5-hydroxytryptamine 3 (5-HT3) antagonist and a corticosteroid, a single 150 mg intravenous (IV) dose of fosaprepitant given on Day 1 is superior to the control regimen of 5-HT3 antagonist and corticosteroid only, in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC).

Conditions

Chemotherapy-Induced Nausea and Vomiting (CINV)

Keywords

NK-1 Receptor Antagonist, CINV, Emesis, MEC

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Complete Response From 25 to 120 Hours After Initiation of Moderately Emetogenic Chemotherapy (MEC)

  A Complete Response was defined as no vomiting and no use of rescue medication.

  25 to 120 hours after initiation of MEC

• Percentage of Participants With Infusion-site Thrombophlebitis

  The percentages of participants with infusion-site thrombophlebitis are presented. Thrombophlebitis was defined as a condition affecting a superficial vein used for an IV infusion, associated with red color, hardness upon palpation, and the presence of a tender cord and possible fever.

  Day 1 through Day 17, inclusive

• Percentage of Participants With Severe Infusion-site Reactions

  The percentages of participants with severe infusion-site reactions, including severe site pain, or severe site redness (erythema) or severe site hardness (induration) are presented.

  Day 1 through Day 17, inclusive

Secondary Outcomes (3)

• Percentage of Participants With Complete Response From 0 to 120 Hours After Initiation of MEC

  0 to 120 hours after initiation of MEC

• Percentage of Participants With Complete Response From 0 to 24 Hours After Initiation of MEC

  0 to 24 hours after initiation of MEC

• Percentage of Participants With No Vomiting From 0 to 120 Hours After Initiation of MEC

  0 to 120 hours after initiation of MEC

Study Arms (2)

Fosaprepitant Regimen

EXPERIMENTAL

On Day 1, participants received fosaprepitant, 150 mg intravenous (IV) infusion, \~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, orally (PO) \~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO \~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO \~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.

Drug: Fosaprepitant dimeglumine; Drug: Dexamethasone; Drug: Ondansetron; Drug: Dexamethasone Placebo; Drug: Ondansetron Placebo; Drug: Rescue Therapy

Control Regimen

ACTIVE COMPARATOR

On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, \~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO \~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO \~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.

Drug: Fosaprepitant Placebo; Drug: Dexamethasone; Drug: Ondansetron; Drug: Rescue Therapy

Interventions

Fosaprepitant dimeglumine DRUG

Also known as: EMEND for Injection, MK-0517

Fosaprepitant Regimen

Fosaprepitant Placebo DRUG

Control Regimen

Dexamethasone DRUG

Also known as: Decadron

Control Regimen; Fosaprepitant Regimen

Ondansetron DRUG

Also known as: Zofran

Control Regimen; Fosaprepitant Regimen

Dexamethasone Placebo DRUG

Fosaprepitant Regimen

Ondansetron Placebo DRUG

Fosaprepitant Regimen

Rescue Therapy DRUG

Control Regimen; Fosaprepitant Regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a histologically or cytologically confirmed malignant disease
• Is naive to moderately and highly emetogenic chemotherapy
• Is scheduled to receive a single IV dose of one or more MEC agents on Day 1, except for the combination of anthracycline and cyclophosphamide
• Has a predicted life expectancy of at least 4 months, and a Karnofsky score of at least 60 indicating that the participant requires occasional assistance, but is able to care for most of his/her needs.
• Female of childbearing potential demonstrates a negative urine pregnancy test, and agrees to remain abstinent or use two acceptable forms of birth control for at least 14 days prior to study, throughout the study, and at least 1 month following last dose of study drug.

You may not qualify if:

• Has vomited in the 24 hours prior to treatment Day 1
• Has symptomatic primary or metastatic symptomatic central nervous system malignancy causing nausea and/or vomiting
• Is scheduled to receive chemotherapy agent classified as highly emetogenic
• Has received or will receive total body irradiation, or radiation therapy to the abdomen, pelvis, head and neck in the week prior to Treatment Days 1 through Day 6 of the Treatment Period
• Has illness or history of illness which might confound study results or pose unwarranted risk
• Known history of QT interval prolongation
• Uses illicit drugs or abuses alcohol
• Mentally incapacitated or has a significant emotional or psychiatric disorder
• History of hypersensitivity to aprepitant, ondansetron or dexamethasone
• Pregnant or breast-feeding
• Has participated in a study with aprepitant or taken a non-approved (investigational) drug within the last 4 weeks
• Has concurrent condition, such as systemic fungal infection or uncontrolled diabetes, that precludes administration of dexamethasone.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (3)

• Weinstein C, Jordan K, Green SA, Camacho E, Khanani S, Beckford-Brathwaite E, Vallejos W, Liang LW, Noga SJ, Rapoport BL. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial. Ann Oncol. 2016 Jan;27(1):172-8. doi: 10.1093/annonc/mdv482. Epub 2015 Oct 8.

  PMID: 26449391 RESULT

• Weinstein C, Jordan K, Green S, Khanani S, Beckford-Brathwaite E, Vallejos W, Pong A, Noga SJ, Rapoport BL. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy regimens: a subgroup analysis from a randomized clinical trial of response in subjects by cancer type. BMC Cancer. 2020 Sep 25;20(1):918. doi: 10.1186/s12885-020-07259-5.

  PMID: 32988373 DERIVED

• Weinstein C, Jordan K, Green SA, Camacho E, Khanani S, Beckford-Brathwaite E, Pong A, Noga SJ, Rapoport BL. Evaluation of factors contributing to the response to fosaprepitant in a heterogeneous, moderately emetogenic chemotherapy population: an exploratory analysis of a randomized phase III trial. Support Care Cancer. 2018 Nov;26(11):3773-3780. doi: 10.1007/s00520-018-4242-x. Epub 2018 May 28.

  PMID: 29808377 DERIVED

MeSH Terms

Conditions

Vomiting

Interventions

fosaprepitant; Aprepitant; Dexamethasone; Calcium Dobesilate; Ondansetron

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Imidazoles; Azoles; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2012
• First Posted: May 9, 2012
• Study Start: September 24, 2012
• Primary Completion: November 3, 2014
• Study Completion: November 3, 2014
• Last Updated: September 4, 2018
• Results First Posted: September 25, 2015

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share