Low Dose Aprepitant for Patients Receiving Carboplatin

NCT03237611 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2015-5109
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

This study evaluates a simple one day prophylaxis of nausea and vomiting for patients who are getting carboplatin based chemotherapy. In addition to standard oral Dexamethasone and oral Ondansetron, participants will be given a third neurokinin 1 (NK1) antagonist agent, either a single dose of oral Aprepitant or intravenous (IV) Fosaprepitant (they have been shown to be equally effective) to improve prevention of nausea and vomiting. No medications need to be taken beyond day 1.

Conditions

Chemotherapy-induced Nausea and Vomiting

Keywords

emesis; aprepitant; carboplatin; chemotherapy-induced nausea and vomiting

Outcome Measures

Primary Outcomes (2)

• Complete Control Rate of Chemotherapy-induced Nausea and Vomiting (CINV) Following 1st Cycle of Chemotherapy

  Complete control rate of nausea and vomiting is defined as the percentage of patients without episodes of nausea or emesis, or rescue medication administered, during the overall phase of the first carboplatin-based chemotherapy cycle. Data was collected by administration of the MASCC Antiemesis Tool. The MASCC Antiemesis Tool is an eight-item questionnaire administered to patients to assess the occurrence of vomiting and nausea both during the first 24 hours after chemotherapy as well as the occurrence of delayed nausea and vomiting from the day after to 120 hours after chemotherapy.

  24 hours following the first cycle of chemotherapy

• Complete Control Rate of Chemotherapy-induced Nausea and Vomiting (CINV) Following 1st Cycle of Chemotherapy

  Complete control rate of nausea and vomiting is defined as the percentage of patients without episodes of nausea or emesis, or rescue medication administered, during the overall phase of the first carboplatin-based chemotherapy cycle. Data was collected by administration of the MASCC Antiemesis Tool. The MASCC Antiemesis Tool is an eight-item questionnaire administered to patients to assess the occurrence of vomiting and nausea both during the first 24 hours after chemotherapy as well as the occurrence of delayed nausea and vomiting from the day after to 120 hours after chemotherapy.

  From 24 to 120 hours following the first cycle of chemotherapy, approximately 5 days

Secondary Outcomes (2)

• Complete Control Rate of Chemotherapy-induced Nausea and Vomiting (CINV) Following 2nd Cycle of Chemotherapy

  24 hours following the second cycle of chemotherapy

• Complete Control Rate of Chemotherapy-induced Nausea and Vomiting (CINV) Following 2nd Cycle of Chemotherapy

  From 24 to 120 hours following the second cycle of chemotherapy, approximately 5 days

Study Arms (1)

low dose aprepitant or fosaprepitant

EXPERIMENTAL

In addition to standard prophylactic antiemetics (Ondansetron 16mg and Dexamethasone 20mg) patients will be given aprepitant 125mg orally or 115mg fosaprepitant intravenously prior to the first cycle of carboplatin-based chemotherapy. No medications will be given afterwards

Drug: Aprepitant 125 mg; Drug: Fosaprepitant 115 MG; Drug: Dexamethasone; Drug: Ondansetron 16 MG

Interventions

Aprepitant 125 mg DRUG

Patient scheduled for the first cycle of carboplatin-based chemotherapy will be offered to receive low doses of aprepitant (125mg of oral aprepitant) or 115mg of fosaprepitant intravenously for prevention of chemotherapy-induced nausea and vomiting

low dose aprepitant or fosaprepitant

Fosaprepitant 115 MG DRUG

Patient scheduled for the first cycle of carboplatin-based chemotherapy will be offered to receive low doses of aprepitant (125mg of oral aprepitant) or 115mg of fosaprepitant intravenously for prevention of chemotherapy-induced nausea and vomiting

low dose aprepitant or fosaprepitant

Dexamethasone DRUG

Dexamethasone will be given as a part of standard CINV prophylaxis for patients receiving carboplatin-based chemotherapy, dosed at 20mg on day 1 of chemotherapy

low dose aprepitant or fosaprepitant

Ondansetron 16 MG DRUG

Ondansetron will be given as a part of standard CINV prophylaxis for patients receiving carboplatin-based chemotherapy, dosed at 16mg on day 1 of chemotherapy

low dose aprepitant or fosaprepitant

Eligibility Criteria

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

You may qualify if:

• No prior chemotherapy
• Confirmed malignancy, scheduled to receive carboplatin monotherapy, or carboplatin in combination with agents of minimal, low, or moderate emetic potential
• Laboratory parameters adequate for chemotherapy

You may not qualify if:

• Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 3 or 4
• Presence of nausea and vomiting or use of major antiemetic agents during the 24 hours before chemotherapy administration
• Patients receiving radiotherapy within 5 days prior to the carboplatin
• Pregnancy or lactation
• Known allergy to any of the 3 antiemetics

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• Jacobi Medical Center: collaborator

Study Sites (2)

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Related Publications (17)

• Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med. 2008 Jun 5;358(23):2482-94. doi: 10.1056/NEJMra0706547. No abstract available.

  PMID: 18525044 BACKGROUND

• Roila F, Herrstedt J, Aapro M, Gralla RJ, Einhorn LH, Ballatori E, Bria E, Clark-Snow RA, Espersen BT, Feyer P, Grunberg SM, Hesketh PJ, Jordan K, Kris MG, Maranzano E, Molassiotis A, Morrow G, Olver I, Rapoport BL, Rittenberg C, Saito M, Tonato M, Warr D; ESMO/MASCC Guidelines Working Group. Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol. 2010 May;21 Suppl 5:v232-43. doi: 10.1093/annonc/mdq194. No abstract available.

  PMID: 20555089 BACKGROUND

• NCCN Guidelines, Antiemesis, Version I.2015

  BACKGROUND

• Tanioka M, Kitao A, Matsumoto K, Shibata N, Yamaguchi S, Fujiwara K, Minami H, Katakami N, Morita S, Negoro S. A randomised, placebo-controlled, double-blind study of aprepitant in nondrinking women younger than 70 years receiving moderately emetogenic chemotherapy. Br J Cancer. 2013 Aug 20;109(4):859-65. doi: 10.1038/bjc.2013.400. Epub 2013 Jul 16.

  PMID: 23860530 BACKGROUND

• Ito Y, Karayama M, Inui N, Kuroishi S, Nakano H, Nakamura Y, Yokomura K, Toyoshima M, Shirai T, Masuda M, Yamada T, Yasuda K, Hayakawa H, Suda T, Chida K. Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy. Lung Cancer. 2014 Jun;84(3):259-64. doi: 10.1016/j.lungcan.2014.03.017. Epub 2014 Mar 27.

  PMID: 24746177 BACKGROUND

• Yahata H, et al. Ann Oncol. 25 (Suppl 4): abstract 1481PD, 2014

  BACKGROUND

• Gralla R, Jordan K, Rapoport B et al. Assessing the magnitude of antiemetic benefit with the addition of the NK1 receptor antagonist (NK1) aprepitant for all platinum agents: analysis of 1,872 patients (pts) in prospective randomized clinical phase III trials (RCTs) [abstract9057]. J Clin Oncol 2010; 28: 9057.

  BACKGROUND

• Hesketh PJ, et al. Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in moderately emetogenic therapy (MEC). J Clin Oncol 33 (Suppl): abstract 9622, 2015

  BACKGROUND

• Navari RM, Reinhardt RR, Gralla RJ, Kris MG, Hesketh PJ, Khojasteh A, Kindler H, Grote TH, Pendergrass K, Grunberg SM, Carides AD, Gertz BJ. Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. L-754,030 Antiemetic Trials Group. N Engl J Med. 1999 Jan 21;340(3):190-5. doi: 10.1056/NEJM199901213400304.

  PMID: 9917226 BACKGROUND

• Roila F, Ruggeri B, Ballatori E, Fatigoni S, Caserta C, Licitra L, Mirabile A, Ionta MT, Massidda B, Cavanna L, Palladino MA, Tocci A, Fava S, Colantonio I, Angelelli L, Ciuffreda L, Fasola G, Zerilli F. Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study. Ann Oncol. 2015 Jun;26(6):1248-1253. doi: 10.1093/annonc/mdv132. Epub 2015 Mar 5.

  PMID: 25743855 BACKGROUND

• Roila F, Ruggeri B, Ballatori E, Del Favero A, Tonato M. Aprepitant versus dexamethasone for preventing chemotherapy-induced delayed emesis in patients with breast cancer: a randomized double-blind study. J Clin Oncol. 2014 Jan 10;32(2):101-6. doi: 10.1200/JCO.2013.51.4547. Epub 2013 Dec 9.

  PMID: 24323030 BACKGROUND

• Grunberg S, Chua D, Maru A, Dinis J, DeVandry S, Boice JA, Hardwick JS, Beckford E, Taylor A, Carides A, Roila F, Herrstedt J. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE. J Clin Oncol. 2011 Apr 10;29(11):1495-501. doi: 10.1200/JCO.2010.31.7859. Epub 2011 Mar 7.

  PMID: 21383291 BACKGROUND

• Lasseter KC, Gambale J, Jin B, Bergman A, Constanzer M, Dru J, Han TH, Majumdar A, Evans JK, Murphy MG. Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol. 2007 Jul;47(7):834-40. doi: 10.1177/0091270007301800. Epub 2007 May 24.

  PMID: 17525168 BACKGROUND

• Aapro M, Fabi A, Nole F, Medici M, Steger G, Bachmann C, Roncoroni S, Roila F. Double-blind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy. Ann Oncol. 2010 May;21(5):1083-8. doi: 10.1093/annonc/mdp584. Epub 2010 Jan 15.

  PMID: 20080830 BACKGROUND

• Ito Y, Tsuda T, Minatogawa H, Kano S, Sakamaki K, Ando M, Tsugawa K, Kojima Y, Furuya N, Matsuzaki K, Fukuda M, Sugae S, Ohta I, Arioka H, Tokuda Y, Narui K, Tsuboya A, Suda T, Morita S, Boku N, Yamanaka T, Nakajima TE. Placebo-Controlled, Double-Blinded Phase III Study Comparing Dexamethasone on Day 1 With Dexamethasone on Days 1 to 3 With Combined Neurokinin-1 Receptor Antagonist and Palonosetron in High-Emetogenic Chemotherapy. J Clin Oncol. 2018 Apr 1;36(10):1000-1006. doi: 10.1200/JCO.2017.74.4375. Epub 2018 Feb 14.

  PMID: 29443652 BACKGROUND

• Geling O, Eichler HG. Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications. J Clin Oncol. 2005 Feb 20;23(6):1289-94. doi: 10.1200/JCO.2005.04.022.

  PMID: 15718327 BACKGROUND

• Aapro M, Rugo H, Rossi G, Rizzi G, Borroni ME, Bondarenko I, Sarosiek T, Oprean C, Cardona-Huerta S, Lorusso V, Karthaus M, Schwartzberg L, Grunberg S. A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol. 2014 Jul;25(7):1328-1333. doi: 10.1093/annonc/mdu101. Epub 2014 Mar 5.

  PMID: 24603643 BACKGROUND

Related Links

• MASCC Antiemetic tool (MAT)

MeSH Terms

Conditions

Vomiting

Interventions

Aprepitant; fosaprepitant; Dexamethasone; 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; Imidazoles; Azoles; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Dr. Richard Gralla
• Organization: Albert Einstein College of Medicine

richard.gralla@nbhn.net

718-918-6235

Study Officials

• Richard Gralla, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patient scheduled for the first cycle of carboplatin-based chemotherapy will be offered to receive 125mg of oral aprepitant or 115mg of fosaprepitant intravenously for prevention of chemotherapy-induced nausea and vomiting

Study Record Dates

• First Submitted: July 31, 2017
• First Posted: August 2, 2017
• Study Start: October 30, 2018
• Primary Completion: February 11, 2021
• Study Completion: February 11, 2021
• Last Updated: November 13, 2023
• Results First Posted: November 13, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)