A Study Of IV Casopitant For The Prevention Of Chemotherapy Induced Nausea And Vomiting.

NCT00601172 | Completed Phase 3 Results

• 1 other identifier: NKV110721
• Study Type: interventional
• Target: 710
• Locations: 11 countries
• Sites: 96

Brief Summary

This a Phase III trial designed to determine if IV casopitant plus dexamethasone and ondansetron is more effective in the prevention of vomiting and nausea then dexamethasone and ondansetrone alone following the administration of moderately emetogenic oxaliplatin-based chemotherapy.

Conditions

Nausea and Vomiting, Chemotherapy-Induced

Keywords

vomiting; colorectal cancer; nausea; oxaliplatin

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved a Complete Response in the Overall Phase (0-120 Hours) Following Initiation of the First Cycle of an Oxaliplatin Based Moderately Emetogenic Chemotherapy (MEC) Regimen

  Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. The overall phase began at the start of the administration of the oxaliplatin infusion. Percentage of participants who achieved a complete response in the overall phase (0-120 hours) are presented.

  0 to 120 hours in the first cycle of chemotherapy

Secondary Outcomes (24)

• Percentage of Participants Who Achieved a Complete Response in the Acute Phase of Cycle 1

  0 to 24 hours in the first cycle of chemotherapy

• Percentage of Participants Who Achieved a Complete Response in the Delayed Phase of Cycle 1

  24 to 120 hours (delayed phase) in the first cycle of chemotherapy

• Percentage of Participants Who Achieved a Complete Response in the Overall Phase of Cycle 2

  0 to 120 hours in the second cycle of chemotherapy

• Maximum Nausea Score, Assessed by a Visual Analogue Scale (VAS)

  0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

• Percentage of Participants Who Received Rescue Medication

  0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

Study Arms (2)

Control

PLACEBO COMPARATOR

Placebo + standard antiemetics

Drug: Dexamethasone; Drug: Placebo; Drug: Ondansetron

Single Dose IV

EXPERIMENTAL

Casopitant + standard antiemetics

Drug: Casopitant; Drug: Dexamethasone; Drug: Ondansetron

Interventions

Casopitant DRUG

Experimental NK-1 receptor antagonist

Single Dose IV

Dexamethasone DRUG

Standard antiemetics

Control; Single Dose IV

Placebo DRUG

Placebo to match IV casopitant

Control

Ondansetron DRUG

Standard antiemetics

Control; Single Dose IV

Eligibility Criteria

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

You may qualify if:

• Subject understands the nature and purpose of this study and the study procedures and has signed an informed consent form for this study to indicate this understanding.
• At least 18 years of age.
• Is scheduled to receive oxaliplatin at a dose between 85 mg/m² and 130 mg/m² in their first cycle of therapy for the treatment of colorectal cancer, administered as a single IV dose over 2-6 hours on Day 1 only, in combination with 5FU/LV, or in combination with capecitabine.
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Hematologic and metabolic status adequate for receiving an oxaliplatin-based moderately emetogenic regimen and meeting the following criteria:
• Total Neutrophils ≥1500/mm³ (Standard units : ≥1.5 x 10\^9/L)
• Platelets ≥100,000/mm³ (Standard units: ≥100.0 x 10\^9/L)
• Bilirubin ≤1.5 x upper limit of normal (ULN)
• Serum Creatinine ≤1.5 mg/dL (Standard units : ≤132.6 µmol/L) OR
• Creatinine clearance ≥60 mL/min
• Creatinine clearance must be calculated using the Cockcroft-Gault formula:
• Clcreat (ml/min) = (140-age \[yr\]) x body wt \[kg\] 72 x serum creatinine \[mg/dl\] For females: multiply creatinine clearance by a factor of 0.85. OR Clcreat (ml/min) = K x (140-age \[yr\]) x body wt \[kg\] serum creatinine \[µmol/L\] K=1.05 for females K=1.23 for males
• Liver enzymes must be below the following limits:
• Without known liver metastases: Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 x ULN.
• With known liver metastases: AST and/or ALT ≤5.0 x ULN.

You may not qualify if:

• Has received cytotoxic chemotherapy prior to the first study cycle of chemotherapy, with the exception that previous adjuvant therapy with 5FU/LV or capecitabine is permitted, provided that the last dose of adjuvant therapy was completed at least 6 months prior to receiving the first dose of study medication or investigational product. Previous biological or hormonal therapy completed at any time is permitted.
• Is a female subject who is pregnant or lactating.
• Has received radiation therapy in the 10 days prior to the first dose of study medication or investigational product and/or is scheduled to receive such radiation therapy in the 6 days following the first dose of study medication or investigational product in the first cycle of chemotherapy. Radiation therapy may be added in subsequent cycles of chemotherapy.
• Has experienced emesis (i.e., vomiting and/or retching) or clinically significant nausea in the 24 hours preceding the first dose of study medication or investigational product for each cycle of chemotherapy.
• Has known central nervous system metastasis, unless previously successfully treated with excision or radiation, and has been stable for at least 1 week immediately prior to receiving the first dose of study medication or investigational product.
• Has increased intracranial pressure, hypercalcemia, an active systemic infection, or any uncontrolled medical condition (other than malignancy) which in the opinion of the Investigator may confound the results of the study, represent another potential etiology for emesis and nausea (other than CINV) or pose an unwarranted risk to the subject.
• Has a known hypersensitivity or contraindication to ondansetron, another 5-HT3 receptor antagonist, dexamethasone, or any component of casopitant.
• Has received an NK-1 receptor antagonist prior to the first study cycle of chemotherapy.
• Has received an investigational drug within the previous 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study medication or investigational product, or is scheduled to receive any investigational drug other than casopitant/placebo during the study period.
• Has taken/received any medication of moderate or high emetogenic potential (including antineoplastic agents \[see Appendix 2\]) within the 48 hours prior to the first dose of study medication or investigational product in each cycle. However, opioid narcotics will be permitted if the subject has been on such medication for at least 7 days at a stable dose prior to the start of each cycle, and has not experienced emesis or nausea from the narcotics.
• Has taken/received any medication with known or potential antiemetic activity within the 24-hour period (unless otherwise stated) prior to receiving the first dose of study medication or investigational product or is expected to require use of such medication during the 120 hour assessment period for Cycle 1 of therapy only. This includes, but is not limited to:
• HT3 receptor antagonists (e.g., additional ondansetron, or granisetron, dolasetron, tropisetron, ramosetron). Palonosetron is not permitted within 7 days prior to administration of study medication or investigational product;
• benzamide / benzamide derivatives (e.g., metoclopramide, alizapride);
• benzodiazepines (except if the subject is receiving such medication for sleep or anxiety and has been on a stable dose for at least 7 days prior to the first dose of investigational product; however, lorazepam is prohibited 24 hours prior to receiving study drug regardless of reason for use);
• phenothiazines (e.g., prochlorperazine, promethazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine);

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (96)

GSK Investigational Site

Hot Springs, Arkansas, 71913, United States

Location

GSK Investigational Site

Corona, California, 92879, United States

Location

GSK Investigational Site

Fountain Valley, California, 92708, United States

Location

GSK Investigational Site

Riverside, California, 92501, United States

Location

GSK Investigational Site

St. Petersburg, Florida, 33705, United States

Location

GSK Investigational Site

Tampa, Florida, 33614, United States

Location

GSK Investigational Site

Alexandria, Louisiana, 71301, United States

Location

GSK Investigational Site

Baton Rouge, Louisiana, 70809, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21215-5271, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02135, United States

Location

GSK Investigational Site

Worcester, Massachusetts, 01608, United States

Location

GSK Investigational Site

Jefferson City, Missouri, 65109, United States

Location

GSK Investigational Site

Great Falls, Montana, 59405, United States

Location

GSK Investigational Site

The Bronx, New York, 10467, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

Location

GSK Investigational Site

Hilton Head Island, South Carolina, 29926, United States

Location

GSK Investigational Site

Mt. Pleasant, South Carolina, 29464, United States

Location

GSK Investigational Site

Sumter, South Carolina, 29150, United States

Location

GSK Investigational Site

Corpus Christi, Texas, 78412, United States

Location

GSK Investigational Site

Corpus Christi, Texas, 78463-3069, United States

Location

GSK Investigational Site

Duncanville, Texas, 75137, United States

Location

GSK Investigational Site

Ogden, Utah, 84403, United States

Location

GSK Investigational Site

Burlington, Vermont, 05401, United States

Location

GSK Investigational Site

Assebroek, 8310, Belgium

Location

GSK Investigational Site

Bonheiden, 2820, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Ottignies, 1340, Belgium

Location

GSK Investigational Site

Shumen, 9700, Bulgaria

Location

GSK Investigational Site

Sofia, 1756, Bulgaria

Location

GSK Investigational Site

Varna, 9010, Bulgaria

Location

GSK Investigational Site

Sault Ste. Marie, Ontario, P6A 2C4, Canada

Location

GSK Investigational Site

Thunder Bay, Ontario, P7B 6V4, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 1X5, Canada

Location

GSK Investigational Site

Charlottetown, Prince Edward Island, C1A 8T5, Canada

Location

GSK Investigational Site

Greenfield Park, Quebec, J4V 2H1, Canada

Location

GSK Investigational Site

Laval, Quebec, H7M 3L9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H1T 2M4, Canada

Location

GSK Investigational Site

Rimouski, Quebec, G5L 5T1, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1H 5N4, Canada

Location

GSK Investigational Site

Brno, 625 00, Czechia

Location

GSK Investigational Site

Brno, 656 91, Czechia

Location

GSK Investigational Site

Chomutov, 430 12, Czechia

Location

GSK Investigational Site

Havlíčkův Brod, 580 22, Czechia

Location

GSK Investigational Site

Prague, 100 00, Czechia

Location

GSK Investigational Site

Prague, 180 81, Czechia

Location

GSK Investigational Site

Semily, 513 01, Czechia

Location

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89081, Germany

Location

GSK Investigational Site

Aschaffenburg, Bavaria, 63739, Germany

Location

GSK Investigational Site

Augsburg, Bavaria, 86150, Germany

Location

GSK Investigational Site

Hof, Bavaria, 95028, Germany

Location

GSK Investigational Site

Munich, Bavaria, 81241, Germany

Location

GSK Investigational Site

Würzburg, Bavaria, 97070, Germany

Location

GSK Investigational Site

Bad Soden, Hesse, 65812, Germany

Location

GSK Investigational Site

Kassel, Hesse, 34119, Germany

Location

GSK Investigational Site

Braunschweig, Lower Saxony, 38114, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30171, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

GSK Investigational Site

Recklinghausen, North Rhine-Westphalia, 45657, Germany

Location

GSK Investigational Site

Würselen, North Rhine-Westphalia, 52146, Germany

Location

GSK Investigational Site

Magdeburg, Saxony-Anhalt, 39104, Germany

Location

GSK Investigational Site

Lübeck, Schleswig-Holstein, 23562, Germany

Location

GSK Investigational Site

Pinneberg, Schleswig-Holstein, 25421, Germany

Location

GSK Investigational Site

Jena, Thuringia, 07743, Germany

Location

GSK Investigational Site

Hamburg, 22081, Germany

Location

GSK Investigational Site

Hamburg, 22457, Germany

Location

GSK Investigational Site

Budapest, 1106, Hungary

Location

GSK Investigational Site

Budapest, 1125, Hungary

Location

GSK Investigational Site

Gyula, 5700, Hungary

Location

GSK Investigational Site

Veszprém, 8200, Hungary

Location

GSK Investigational Site

Potenza, Basilicate, 85100, Italy

Location

GSK Investigational Site

Rionero in Vulture (PZ), Basilicate, 85028, Italy

Location

GSK Investigational Site

Reggio Calabria, Calabria, 89125, Italy

Location

GSK Investigational Site

Avellino, Campania, 83100, Italy

Location

GSK Investigational Site

Benevento, Campania, 82100, Italy

Location

GSK Investigational Site

Napoli, Campania, 80131, Italy

Location

GSK Investigational Site

Genoa, Liguria, 16132, Italy

Location

GSK Investigational Site

Sassari, Sardinia, 07100, Italy

Location

GSK Investigational Site

Catania, Sicily, 95125, Italy

Location

GSK Investigational Site

Florence, Tuscany, 50139, Italy

Location

GSK Investigational Site

Terni, Umbria, 05100, Italy

Location

GSK Investigational Site

Padua, Veneto, 35128, Italy

Location

GSK Investigational Site

Kazan', 420029, Russia

Location

GSK Investigational Site

Moscow, 115478, Russia

Location

GSK Investigational Site

Moscow, 129 128, Russia

Location

GSK Investigational Site

Moscow Region, 143 423, Russia

Location

GSK Investigational Site

Saint Petersburg, 197758, Russia

Location

GSK Investigational Site

Samara, 443066, Russia

Location

GSK Investigational Site

Banská Bystrica, 975 17, Slovakia

Location

GSK Investigational Site

Bratislava, 833 10, Slovakia

Location

GSK Investigational Site

Košice, 041 91, Slovakia

Location

GSK Investigational Site

Poprad, 058 01, Slovakia

Location

GSK Investigational Site

Gyeonggi-do, 410-769, South Korea

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Seoul, 135-710, South Korea

Location

GSK Investigational Site

Songpa-gu, Seoul, 138-736, South Korea

Location

Related Publications (1)

• Hesketh PJ, Wright O, Rosati G, Russo M, Levin J, Lane S, Moiseyenko V, Dube P, Kopp M, Makhson A. Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, active-controlled, two arm, parallel group study. Support Care Cancer. 2012 Jul;20(7):1471-8. doi: 10.1007/s00520-011-1235-4. Epub 2011 Aug 7.

  PMID: 21822913 BACKGROUND

MeSH Terms

Conditions

Nausea; Vomiting; Colorectal Neoplasms

Interventions

casopitant; Dexamethasone; Ondansetron

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  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: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2008
• First Posted: January 25, 2008
• Study Start: March 10, 2008
• Primary Completion: April 13, 2009
• Study Completion: April 13, 2009
• Last Updated: January 17, 2018
• Results First Posted: January 17, 2018

Record last verified: 2017-11

Locations

SL (4); IT (12); BU (3); CA (9); CZ (7); BE (4); RU (6); DE (20); HU (4); KR (4); US (23)