Basic Trial Information
Trial Description
     Summary
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Supportive care, Treatment Active 18 and over Pharmaceutical / Industry NKV110721 NCT00601172

Trial Description

Summary

This a Phase III trial designed to demonstrate that 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 chemotherapy.

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.

Trial Contact Information

Trial Lead Organizations/Sponsors

GlaxoSmithkline

GSK Clinical Trials, MD, PhD

Study Director

US GSK Clinical Trials Call Center

Ph: 877-379-3718

U.S.A.
Arkansas
	Hot Springs
	GSK Investigational Site
California
	Corona
	GSK Investigational Site
	Fountain Valley
	GSK Investigational Site
	Riverside
	GSK Investigational Site
Florida
	St Petersburg
	GSK Investigational Site
	Tampa
	GSK Investigational Site
Louisiana
	Alexandria
	GSK Investigational Site
	Baton Rouge
	GSK Investigational Site
Massachusetts
	Boston
	GSK Investigational Site
	Worcester
	GSK Investigational Site
Missouri
	Jefferson City
	GSK Investigational Site
Montana
	Great Falls
	GSK Investigational Site
North Carolina
	Winston-Salem
	GSK Investigational Site
South Carolina
	Hilton Head Island
	GSK Investigational Site
	Mt. Pleasant
	GSK Investigational Site
	Sumter
	GSK Investigational Site
Texas
	Corpus Christi
	GSK Investigational Site
	Duncanville
	GSK Investigational Site
Utah
	Ogden
	GSK Investigational Site
Vermont
	Burlington
	GSK Investigational Site
Belgium
	Assebroek
	GSK Investigational Site
	Bonheiden
	GSK Investigational Site
	Gent
	GSK Investigational Site
	Ottignies
	GSK Investigational Site
Canada
	Charlottetown
	GSK Investigational Site
Ontario
	Sault Ste. Marie
	GSK Investigational Site
	Thunder Bay
	GSK Investigational Site
	Toronto
	GSK Investigational Site
Quebec
	Greenfield Park
	GSK Investigational Site
	Laval
	GSK Investigational Site
	Montreal
	GSK Investigational Site
	Rimouski
	GSK Investigational Site
	Sherbrooke
	GSK Investigational Site
Czech Republic
	Brno
	GSK Investigational Site
	Chomutov
	GSK Investigational Site
	Havlickuv Brod
	GSK Investigational Site
	Praha 10
	GSK Investigational Site
	Praha 8
	GSK Investigational Site
	Semily
	GSK Investigational Site
Germany
	Aschaffenburg
	GSK Investigational Site
	Bad Soden
	GSK Investigational Site
	Freiburg
	GSK Investigational Site
	Hamburg
	GSK Investigational Site
	Hannover
	GSK Investigational Site
	Hof
	GSK Investigational Site
	Jena
	GSK Investigational Site
	Kassel
	GSK Investigational Site
	Luebeck
	GSK Investigational Site
	Magdeburg
	GSK Investigational Site
	Muenchen
	GSK Investigational Site
	Wuerselen
	GSK Investigational Site
	Wuerzburg
	GSK Investigational Site
Hungary
	Budapest
	GSK Investigational Site
	Gyula
	GSK Investigational Site
	Veszprém
	GSK Investigational Site
Italy
	Avellino
	GSK Investigational Site
	Benevento
	GSK Investigational Site
	Catania
	GSK Investigational Site
	Firenze
	GSK Investigational Site
	Genova
	GSK Investigational Site
	Napoli
	GSK Investigational Site
	Padova
	GSK Investigational Site
	Potenza
	GSK Investigational Site
	Reggio Calabria
	GSK Investigational Site
	Rionero in Vulture (PZ)
	GSK Investigational Site
	Sassari
	GSK Investigational Site
	Terni
	GSK Investigational Site
Republic of Bulgaria
	Shumen
	GSK Investigational Site
	Sofia
	GSK Investigational Site
	Varna
	GSK Investigational Site
Republic of Korea
	Gyeonggi-do
	GSK Investigational Site
	Seoul
	GSK Investigational Site
	songpa-gu, Seoul
	GSK Investigational Site
Russia
	Kazan
	GSK Investigational Site
	Moscow
	GSK Investigational Site
	Moscow Region
	GSK Investigational Site
	Samara
	GSK Investigational Site
	St. Petersburg
	GSK Investigational Site
Slovakia
	Banska Bystrica
	GSK Investigational Site
	Bratislava
	GSK Investigational Site
	Kosice
	GSK Investigational Site
	Poprad
	GSK Investigational Site

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00601172
Information obtained from ClinicalTrials.gov on October 16, 2008