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

NCT ID: NCT00601172

Last Updated: 2018-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 710 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-10
• Study Completion Date: 2009-04-13

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

Control

Placebo + standard antiemetics

Group Type: PLACEBO_COMPARATOR

Dexamethasone

Intervention Type: DRUG

Standard antiemetics

Placebo

Intervention Type: DRUG

Placebo to match IV casopitant

Ondansetron

Intervention Type: DRUG

Standard antiemetics

Single Dose IV

Casopitant + standard antiemetics

Group Type: EXPERIMENTAL

Casopitant

Intervention Type: DRUG

Experimental NK-1 receptor antagonist

Dexamethasone

Intervention Type: DRUG

Standard antiemetics

Ondansetron

Intervention Type: DRUG

Standard antiemetics

Interventions

Casopitant

Experimental NK-1 receptor antagonist

Intervention Type: DRUG

Dexamethasone

Standard antiemetics

Intervention Type: DRUG

Placebo

Placebo to match IV casopitant

Intervention Type: DRUG

Ondansetron

Standard antiemetics

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• A subject will be considered eligible for initial inclusion in this study, and progression into subsequent cycles of therapy within the study, only if all of the following criteria apply:
• 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.

• Is willing and able to complete daily components of the Subject Diary for Cycle 1 and Cycle 2 without assistance from others.
• A female subject is eligible to enter and participate in this study if she is of:

1. non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal. For purposes of this study, postmenopausal is defined as one year without menses)

2. child-bearing potential: must have a negative serum pregnancy test result or negative urine dipstick pregnancy test within 24 hours prior to the first dose of investigational product on Cycle 1 Day 1. Women of childbearing potential must also commit to consistent and correct use of an acceptable method of birth control. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:

• male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject;
• oral contraceptives (e.g., oral, injectable, or implantable) with double-barrier method of contraception consisting of spermicide with either condom or diaphragm for a period after the trial to account for a potential drug interaction (minimum of six weeks);
• double-barrier method of contraception consisting of spermicide with either condom or diaphragm;
• intra-uterine device with a documented failure rate of less than 1% per year;
• complete abstinence from intercourse for two weeks before exposure to the investigational product throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of 3 days);
• if subject indicates they will remain abstinent during the period described above, they must agree to follow GSK guidelines for the consistent and correct use of an acceptable method of birth control should they become sexually active.

Exclusion Criteria

• A subject will not be eligible for initial inclusion in this study if any of the following criteria apply, or will not be eligible for subsequent cycles of therapy if any of the following criteria become applicable:
• 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.
• Scheduled to receive chemotherapy with any cytotoxic agents (e.g., irinotecan, gemcitabine) or biological agents (e.g., cetuximab, panitumimab) other than the protocol allowed chemotherapy described in Inclusion Criterion 3.
• 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:

• 5-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);
• butyrophenones (e.g., haloperidol, droperidol);
• corticosteroids within 72 hours prior to the first dose of study medication or investigational product (e.g., dexamethasone, methylprednisolone); with the exception that topical steroids for skin disorders including eye and ear drops, and inhaled steroids for respiratory disorders at ≤ 10 mg prednisone daily or its equivalent are permitted;
• anticholinergics (e.g., scopolamine); with the exception that anticholinergics for the treatment of respiratory disorders and the management of diarrhea (e.g., ipratropium bromide, and hyoscyamine) and anticholinergic eye drops are permitted;
• first-generation antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine; see Appendix 4); except for topical use which is permitted;
• domperidone;
• cannabinoids;
• mirtazapine;
• olanzapine.
• Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 for a specified period prior to administration of investigational product in each cycle of therapy.
• Has taken/received inducers of CYP3A4 and CYP3A5 within 14 days prior to the administration of investigational product in each cycle of therapy.
• Is currently taking, or plans to take the following CYP2C8 substrates at any time during the study: the anti-diabetic agent repaglinide or the diuretic torsemide.
• Is currently taking, or plans to take any of the following CYP3A4 substrates at any time during the study: astemizole, cisapride, pimozide, terfenadine.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Hot Springs, Arkansas, United States

GSK Investigational Site

Corona, California, United States

GSK Investigational Site

Fountain Valley, California, United States

GSK Investigational Site

Riverside, California, United States

GSK Investigational Site

St. Petersburg, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Alexandria, Louisiana, United States

GSK Investigational Site

Baton Rouge, Louisiana, United States

GSK Investigational Site

Baltimore, Maryland, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Worcester, Massachusetts, United States

GSK Investigational Site

Jefferson City, Missouri, United States

GSK Investigational Site

Great Falls, Montana, United States

GSK Investigational Site

The Bronx, New York, United States

GSK Investigational Site

Winston-Salem, North Carolina, United States

GSK Investigational Site

Hilton Head Island, South Carolina, United States

GSK Investigational Site

Mt. Pleasant, South Carolina, United States

GSK Investigational Site

Sumter, South Carolina, United States

GSK Investigational Site

Corpus Christi, Texas, United States

GSK Investigational Site

Corpus Christi, Texas, United States

GSK Investigational Site

Duncanville, Texas, United States

GSK Investigational Site

Ogden, Utah, United States

GSK Investigational Site

Burlington, Vermont, United States

GSK Investigational Site

Assebroek, , Belgium

GSK Investigational Site

Bonheiden, , Belgium

GSK Investigational Site

Ghent, , Belgium

GSK Investigational Site

Ottignies, , Belgium

GSK Investigational Site

Shumen, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Varna, , Bulgaria

GSK Investigational Site

Sault Ste. Marie, Ontario, Canada

GSK Investigational Site

Thunder Bay, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Charlottetown, Prince Edward Island, Canada

GSK Investigational Site

Greenfield Park, Quebec, Canada

GSK Investigational Site

Laval, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Rimouski, Quebec, Canada

GSK Investigational Site

Sherbrooke, Quebec, Canada

GSK Investigational Site

Brno, , Czechia

GSK Investigational Site

Brno, , Czechia

GSK Investigational Site

Chomutov, , Czechia

GSK Investigational Site

Havlíčkův Brod, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Semily, , Czechia

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, Germany

GSK Investigational Site

Ulm, Baden-Wurttemberg, Germany

GSK Investigational Site

Aschaffenburg, Bavaria, Germany

GSK Investigational Site

Augsburg, Bavaria, Germany

GSK Investigational Site

Hof, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Würzburg, Bavaria, Germany

GSK Investigational Site

Bad Soden, Hesse, Germany

GSK Investigational Site

Kassel, Hesse, Germany

GSK Investigational Site

Braunschweig, Lower Saxony, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Recklinghausen, North Rhine-Westphalia, Germany

GSK Investigational Site

Würselen, North Rhine-Westphalia, Germany

GSK Investigational Site

Magdeburg, Saxony-Anhalt, Germany

GSK Investigational Site

Lübeck, Schleswig-Holstein, Germany

GSK Investigational Site

Pinneberg, Schleswig-Holstein, Germany

GSK Investigational Site

Jena, Thuringia, Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Gyula, , Hungary

GSK Investigational Site

Veszprém, , Hungary

GSK Investigational Site

Potenza, Basilicate, Italy

GSK Investigational Site

Rionero in Vulture (PZ), Basilicate, Italy

GSK Investigational Site

Reggio Calabria, Calabria, Italy

GSK Investigational Site

Avellino, Campania, Italy

GSK Investigational Site

Benevento, Campania, Italy

GSK Investigational Site

Napoli, Campania, Italy

GSK Investigational Site

Genoa, Liguria, Italy

GSK Investigational Site

Sassari, Sardinia, Italy

GSK Investigational Site

Catania, Sicily, Italy

GSK Investigational Site

Florence, Tuscany, Italy

GSK Investigational Site

Terni, Umbria, Italy

GSK Investigational Site

Padua, Veneto, Italy

GSK Investigational Site

Kazan', , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow Region, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Samara, , Russia

GSK Investigational Site

Banská Bystrica, , Slovakia

GSK Investigational Site

Bratislava, , Slovakia

GSK Investigational Site

Košice, , Slovakia

GSK Investigational Site

Poprad, , Slovakia

GSK Investigational Site

Gyeonggi-do, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Songpa-gu, Seoul, , South Korea

Countries

United States; Belgium; Bulgaria; Canada; Czechia; Germany; Hungary; Italy; Russia; Slovakia; South Korea

References

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.

Reference Type: BACKGROUND

PMID: 21822913 (View on PubMed)

Other Identifiers

NKV110721

Identifier Type: -

Identifier Source: org_study_id