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A Study of the Drug Casopitant for the Prevention of Nausea Caused By Cisplatin-Based Highly Emetogenic Chemotherapy

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00431236
First received: February 2, 2007
Last updated: October 13, 2010
Last verified: October 2010
  Purpose

This is a Phase III trial designed to demonstrate that casopitant when added to dexamethasone and ondansetron is more effective in the prevention of vomiting then dexamethasone and ondansetron alone, in patients who receive a cisplatin-based highly emetogenic chemotherapy.


Condition Intervention Phase
Nausea
Vomiting
Drug: Oral Casopitant (GW679769)
Drug: IV Casopitant (GW679769)
Drug: IV ondansetron hydrochloride
Drug: Oral dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: See Detailed Description

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To demonstrate that triple therapy casopitant, ondansetron and dexamethasone provides an improved CR rate over ZOFRAN and dexamethasone alone during the 120 hours following a cisplatin-based HEC regimen. [ Time Frame: 120 Hours ]

Secondary Outcome Measures:
  • If a subject withdraws prematurely during the first 120 hours, then the time of withdrawal will be considered to be their time to first use of antiemetic rescue medications, and will be censored.
  • Time to first emetic event, defined as the time elapsed from the start of administration of HEC to the first emetic episode.
  • If a subject withdraws prematurely during the first 120 hours, then the time of withdrawal will be considered to be their first emetic episode, and will be censored.
  • The proportion of subjects who receive rescue medication.
  • The proportion of subjects reporting significant nausea defined as a maximum nausea score greater than or equal to 25 mm on the VAS.
  • The proportion of subjects reporting nausea defined as a maximum nausea score greater than or equal to 5 mm on the VAS.
  • The proportion of subject achieving total control, defined as complete responders who had no nausea.
  • The impact on subjects' daily life activities for the first 120 hours following the first cycle of chemotherapy as assessed by the FLIE questionnaire.
  • Subject satisfaction with the prophylactic antiemetic regimens, and the willingness of subjects to use the same treatment during future chemotherapy, as assessed by the Subject Satisfaction\Willingness Assessment in the Subject Diary.
  • Nausea as assessed by a categorical scale, over the first 120 hours following HEC administration.
  • Assessment of the safety and tolerability of casopitant through: routine physical exam, routine clinical laboratory tests, clinical monitoring and adverse events reporting.
  • The proportion of subjects who vomit/retch.
  • The proportion of subjects achieving complete protection, defined as complete responders who had no significant nausea.
  • Complete response over 120 hours following subsequent chemotherapy cycles Use of rescue medication over 120 hours following all chemotherapy cycles Impact on daily life activities over 120 hours, assessed using a subject diary questionnaire [ Time Frame: 120 Hours ]
  • The proportion of subjects who achieve a complete response during the acute (0-24 hrs.) and the delayed (24-120 hrs.) phase following the first cycle of HEC
  • The proportion of subjects who achieve a complete response over the first 120 hours, during the acute (0-24 hrs.), the delayed (24-120 hrs.), and the overall (0-120 hrs.) phase following subsequent cycles of HEC.
  • Maximum nausea score (to assess the severity of nausea), as assessed by a Visual Analogue Scale (VAS) over the first 120 hours and in the acute and delayed phases following each cycle of HEC.
  • Time to first antiemetic rescue medication, defined as the time elapsed from the start of the HEC regimen to the first use of antiemetic rescue medication.

Estimated Enrollment: 810
Study Start Date: November 2006
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Oral Casopitant (GW679769) Drug: IV Casopitant (GW679769) Drug: IV ondansetron hydrochloride Drug: Oral dexamethasone
    Other Names:
    • Oral Casopitant (GW679769)
    • IV Casopitant (GW679769)
    • IV ondansetron hydrochloride
    • Oral dexamethasone
Detailed Description:

A Phase III Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel Group Study of the Efficacy and Safety of the Intravenous and Oral Formulations of the Neurokinin-1 Receptor Antagonist, Casopitant, administered in Combination with ZOFRAN and Dexamethasone for Prevention of Chemotherapy-Induced Nausea and Vomiting in Cancer Subjects Receiving Highly Emetogenic Cisplatin-Based Chemotherapy

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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.
  • Males or females of at least 18 years of age.
  • Diagnosed with a malignant solid tumor and is scheduled to receive their first course of cytotoxic chemotherapy with cisplatin administered as a single intravenous dose of ≥ 70mg/m² over 1-4 hours on study Day 1, either alone or in combination with other chemotherapeutic agents. For combination regimens, non-cisplatin agents of moderate to high emetogenic potential will be allowed, but must be administered following the cisplatin infusion and be completed no more than 6 hours after the initiation of the cisplatin infusion. Chemotherapy agents of minimal to low emetogenic potential may be given on Day 1 following cisplatin or on any subsequent study day. Taxanes (e.g. paclitaxel, docetaxel) may be administered on study Day 1 only following cisplatin.
  • Has an ECOG Performance Status of 0, 1, or 2.
  • Hematologic and metabolic status must be adequate for receiving a highly emetogenic cisplatin-based regimen and meet the following criteria:

    • Total Neutrophils ≥ 1500/mm³ (Standard units : ≥1.5 x 10^9/L)
    • Platelets ≥ 100,000/mm (Standard units: ≥100.0 x 10^9/L)
    • Bilirubin ≤ 1.5 x 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) = (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 upper limit of normal.
  • With known liver metastases: AST and/or ALT ≤ 5.0 x upper limit of normal.

    • Is willing and able to complete daily components of the subject diary for each study cycle.
    • Women of childbearing potential; must 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 a physician, are as follows:

      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 of cycle 1 day 1, and agrees to one of the following:
  • 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 (IUD) 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 three days)
  • if subjects indicate 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.

obstruction

Exclusion criteria:

  • Has previously received cytotoxic chemotherapy. Previous biological or hormonal therapy will be permitted.
  • Is scheduled to receive cisplatin treatment on more than one day during a single cycle of therapy.
  • If female, is pregnant or lactating.
  • Has received radiation therapy to the thorax, head & neck, abdomen, or the pelvis in the 10 days prior to receiving the first dose of study medication and/or will receive radiation therapy to the thorax, head & neck, abdomen or the pelvis in the 6 days following the first dose of study medication.
  • Emesis (i.e. vomiting and/or retching) experienced in the 24 hours prior to receiving the first dose of study medication.
  • Clinically significant nausea (e.g. ≥25 mm on a VAS) in the 24 hours prior to receiving the first dose of study medication.
  • A known central nervous system primary or malignancy metastatic to the CNS, unless successfully treated with excision or radiation and subsequently has been stable for at least 1 week prior to receiving the first dose of study medication.
  • Has history of documented peptic ulcer disease (via endoscopy or x-ray), active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, 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 ZOFRAN, another 5-HT3 receptor antagonist, dexamethasone, or any component of casopitant.
  • Has previously received an NK-1 receptor antagonist.
  • An active systemic infection or any uncontrolled disease (other than malignancy) which, in the opinion of the investigator, may confound the results of the study or pose an unwarranted risk to the subject. Subjects with a previous, but not current, history of alcoholism may be permitted provided that, in the investigator's opinion, the subject's disease state will not confound the results of the study.
  • Receiving or planning to receive a systemic corticosteroid therapy at any dose within 72 hours prior to the first dose of study medication, except where indicated as premedication for a taxane. However, topical steroids and inhaled corticosteroids with a steroid dose of≤10 mg prednisone daily or its equivalent are permitted.
  • Is scheduled to receive bone marrow transplantation and/or stem cell rescue with this course of cisplatin therapy.
  • Has received an investigational drug within the 30 days or five half-lives (whichever is longer) prior to receiving the first dose of study medication, and/or is scheduled to receive any investigational drug during the study.
  • Has received moderately and/or highly emetogenic medication within the 48 hours prior to the first dose of study medication. (Opioid narcotics for cancer pain will be permitted if the subject has been on such medication for at least 7 days and has not experienced nausea or emesis from the narcotics.)
  • Has taken/received any medication with known or potential antiemetic activity within the 24-hour period prior to receiving study drug. This includes, but is not limited to:

    • 5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron). Palonestron is not permitted within 7 days prior to administration of 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 seven days prior to the first dose of GW679769 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)
    • butyrophenone (e.g., haloperidol, droperidol)
    • corticosteroids (e.g., dexamethasone, methylprednisolone; with the exception of topical steroids for skin disorders, inhaled steroids for respiratory disorders, and prophylactic treatment for taxane or pemetrexed therapy)
    • anticholinergics (e.g., scopolamine with the exception of inhaled anticholingerics for respiratory disorders e.g., ipratropium bromide)
    • antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine), except for prophylactic use for taxane therapy
    • domperidone
    • mirtazapine
    • olanzapine
    • cannabinoids
  • Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 prior to administration of casopitant (GW679769) investigational product
  • Has taken/received inducers of CYP3A4 and CYP3A5 within fourteen days prior to the administration of casopitant investigational product
  • Is taking the anti-diabetic agent repaglinide or the diuretic torsemide. Investigators are advised to exercise caution if including patients taking the anti-diabetic agents rosiglitazone or pioglitazone, or antimalarial agents such as chloroquine and amodiaquine, as the metabolite of casopitant is a potential inhibitor of CYP2C8
  • Is currently taking or plans to take any of the following CYP3A4 substrates: 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: NCT00431236

  Show 78 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MD GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00431236     History of Changes
Other Study ID Numbers: NKV102551
Study First Received: February 2, 2007
Last Updated: October 13, 2010
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Poland: Ministry of Health
Korea: Food and Drug Administration
Mexico: Ministry of Health

Keywords provided by GlaxoSmithKline:
highly emetogenic
cisplatin
CINV

Additional relevant MeSH terms:
Nausea
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
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 24, 2014