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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00601172
First received: January 15, 2008
Last updated: January 4, 2013
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Nausea and Vomiting
Nausea and Vomiting, Chemotherapy-Induced
Drug: Casopitant
Drug: Dexamethasone and Ondansetron
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: A Study of Single Dose Intravenous Casopitant in Combination With Ondansetron and Dexamethasone for the Prevention of Oxaliplatin Induced Nausea and Vomiting.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Complete response (no vomiting and no use of rescue medication) assessed via subject diary completed during cycle 1, that records vomiting and the use of rescue medication. [ Time Frame: First 120 hours in the first cycle of chemotherapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response during cycle 2. [ Time Frame: First 120 hours in the second cycle of chemotherapy ] [ Designated as safety issue: No ]
  • The proportion of subjects who achieve a complete response in the acute and delayed phases of Cycle 1. [ Time Frame: The first 24 hours (acute phase) and 24-120 hours (delayed phase) after chemotherapy in Cycle 1 ] [ Designated as safety issue: No ]
  • Assessed in the overall, acute and delayed phases of Cycle 1: [ Time Frame: For 5 consecutive days in the first cycle of chemotherapy ] [ Designated as safety issue: No ]
  • Maximum nausea score, assessed by a Visual Analogue Scale (VAS). • The proportion of subjects who receive rescue medication. • The proportion of subjects who vomit/retch. [ Time Frame: For 5 consecutive days in the first cycle of chemotherapy ] [ Designated as safety issue: No ]
  • The proportion of subjects reporting significant nausea, defined as a maximum nausea score ≥ 25 mm on the VAS. • The proportion of subjects reporting nausea, defined as a maximum nausea score ≥ 5 mm on the VAS. [ Time Frame: For 5 consecutive days in the first cycle of chemotherapy ] [ Designated as safety issue: No ]
  • The proportion of subjects achieving complete protection, defined as complete responders who had no significant nausea. [ Time Frame: For 5 consecutive days in the first cycle of chemotherapy ] [ Designated as safety issue: No ]
  • The proportion of subjects achieving total control, defined as complete responders who had no nausea. • Time to first anti-emetic rescue medication. • Time to first emetic event. [ Time Frame: For 5 consecutive days in the first cycle of chemotherapy ] [ Designated as safety issue: No ]
  • Time to event is defined as the time elapsed from the start of the oxaliplatin infusion to the first event. [ Time Frame: For 5 consecutive days in the first cycle of chemotherapy ] [ Designated as safety issue: No ]
  • If a subject withdraws prematurely or dies during the first 120 hours, then the time of withdrawal or death will be considered to be their time to first event, and will be censored. [ Time Frame: For 5 consecutive days in the first cycle of chemotherapy ] [ Designated as safety issue: No ]
  • Health Outcomes Endpoints assessed in Cycle 1: • The impact on subjects' daily life activities in the overall phase, as assessed by the FLIE questionnaire. [ Time Frame: For 5 consecutive days in the first cycle of chemotherapy ] [ Designated as safety issue: No ]
  • Severity of nausea in the overall, acute, and delayed phases assessed by a categorical scale. [ Time Frame: For 5 consecutive days in the first cycle of chemotherapy ] [ Designated as safety issue: No ]
  • PK Endpoints assessed in Cycle 1 (subset of subjects only) [ Time Frame: For up to 48 hours following chemotherapy in cycle 1 ] [ Designated as safety issue: No ]
  • Single-dose pharmacokinetic parameters: AUC(0-∞), AUC(0-t), Cmax, tmax, t1/2 for casopitant and metabolites GSK525060, GSK517142 and GSK631832; and CL and Vdss for casopitant only. [ Time Frame: For 5 consecutive days in the first cycle of chemotherapy ] [ Designated as safety issue: No ]

Enrollment: 710
Study Start Date: March 2008
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control
Placebo + standard antiemetics
Drug: Dexamethasone and Ondansetron
Standard antiemetics
Drug: Placebo
Placebo to match IV casopitant
Experimental: Single Dose IV
Casopitant + standard antiemetics
Drug: Casopitant
Experimental NK-1 receptor antagonist
Drug: Dexamethasone and Ondansetron
Standard antiemetics

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601172

  Show 90 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00601172     History of Changes
Other Study ID Numbers: NKV110721
Study First Received: January 15, 2008
Last Updated: January 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
vomiting
colorectal cancer
nausea
oxaliplatin

Additional relevant MeSH terms:
Nausea
Vomiting
Signs and Symptoms
Signs and Symptoms, Digestive
BB 1101
Casopitant
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Ondansetron
Anti-Anxiety Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antipruritics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dermatologic Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on November 20, 2014