Last updated: 11/04/2018 09:48:01
Intravenous And Oral Casopitant (GW679769) For The Prevention Of Chemotherapy Induced Nausea And Vomiting
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Phase III, Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group Study of the Safety and Efficacy of the Intravenous and Oral Formulations of the Neurokinin-1 Receptor Antagonist Casopitant (GW679769) in Combination with Ondansetron and Dexamethasone for the Prevention of Nausea
Trial description: This is a Phase III trial designed to demonstrate that casopitant (GW679769) plus dexamethasone and ondansetron is more effective in the prevention of vomiting than dexamethasone and ondansetron alone following the administration of moderately emetogenic chemotherapy.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Number of participants who achieved a complete response over the first 120 hours following the initiation of their first cycle of an anthracycline and cyclophosphamide containing MEC regimen
Timeframe: Overall phase (0-120 Hours) of Cycle 1
Secondary outcomes:
Number of participants who achieved a complete response during the acute (0-24 hours) and the delayed (24-120 hours) phase following the first cycle of MEC.
Timeframe: Acute phase (0-24 hours) and delayed phase (24-120 hours) of Cycle 1
Number of participants who achieved a complete response during overall (0-120 hours) phase following the second cycle of MEC
Timeframe: Overall phase (0-120 Hours) of Cycle 2
Number of participants who achieved a complete response during overall (0-120 hours) phase following the third cycle of MEC
Timeframe: Overall phase (0-120 hours) of Cycle 3
Number of participants who achieved a complete response during overall (0-120 hours) phase following the fourth cycle of MEC
Timeframe: Overall phase (0-120 hours) of Cycle 4
Maximum nausea score (MNS) as assessed by a Visual Analogue Scale (VAS) during the acute (0-24 hours) phase
Timeframe: Acute phase (0-24 hours)
MNS as assessed by a VAS during the delayed (24-120 hours) phase
Timeframe: Delayed phase (24-120 hours)
MNS as assessed by a VAS over the first 120 hours
Timeframe: Overall phase (0-120 hours)
Number of participants with time to first antiemetic rescue medication use during the 120 hour assessment phase of each study cycle
Timeframe: Overall phase (0-120 hour) of each cycle
Number of participants with time to first emetic event (vomiting/retching) during the 120 hour assessment phase of each study cycle
Timeframe: Overall phase (0 to 120 hour) of each cycle
Number of participants who required rescue medication over 0-120 hours following Cycle 1 of MEC
Timeframe: Overall phase (0-120 hours) following Cycle 1 of MEC
Number of participants who experienced vomiting/retching over the first 120 hours, during the acute phase (0-24 hours) and the delayed (24-120 hours) phase following Cycle 1 of MEC
Timeframe: Acute phase (0-24 hours), delayed phase (24-120 hours) and Overall phase (0-120 hours) following Cycle 1 of MEC
Number of participants who reported significant nausea (SN) over the first 120 hours, during the acute phase (0-24 hours) and the delayed (24-120 hours) phase following Cycle 1 of MEC
Timeframe: Acute phase (0-24 hours), delayed phase (24-120 hours) and Overall phase (0-120 hours) following Cycle 1 of MEC
Number of participants who reported nausea over the first 120 hours, during the acute phase (0-24 hours) and the delayed (24-120 hours) phase following Cycle 1 of MEC
Timeframe: Acute phase (0-24 hours), delayed phase (24-120 hours) and Overall phase (0-120 hours) following Cycle 1 of MEC
Number of participants who achieved complete protection (CP) over the first 120 hours, during the acute phase (0-24 hours) and the delayed (24-120 hours) phase following Cycle 1 of MEC
Timeframe: Acute phase (0-24 hours), delayed phase (24-120 hours) and Overall phase (0-120 hours) following Cycle 1 of MEC
Number of participants who achieved total control (TC) over the first 120 hours, during the acute phase (0-24 hours) and the delayed (24-120 hours) phase following Cycle 1 of MEC
Timeframe: Acute phase (0-24 hours), delayed phase (24-120 hours) and Overall phase (0-120 hours) following Cycle 1 of MEC
The impact on participants daily life activities for the first 120 hours as assessed by the Functional Living Index-Emesis (FLIE) questionnaire
Timeframe: Overall phase (0-120 hours)
Participant satisfaction (PS) with the prophylactic antiemetic regimens, and the willingness of participants (WP) to use the same treatment during future chemotherapy, assessed by the PS\WP in the Participant Diary over the first 120 hours
Timeframe: Overall phase (0-120 hours)
Number of participants with nausea as assessed by a categorical scale over the first 120 hours during the acute phase (0-24 hours) and the delayed (24-120 hours) phase
Timeframe: Acute phase (0-24 hours), delayed phase (24-120 hours) and overall phase (0-120 hours)
Number of participants with adverse events (AE) and serious adverse events (SAE)
Timeframe: Upto Day 17 of Cycle 1
Number of participants with chemistry grade shifts from Baseline to toxicity grade 3 and 4
Timeframe: Day 1, Day 6-10 and End of cycle visit (Day 17) for Cycle 1-4
Number of participants with hematology toxicity grade shifts from Baseline to toxicity grade 3 and 4
Timeframe: Day 1, Day 6-10 and End of cycle visit (Day 17) for Cycle 1-4
Summary of vital signs-systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Timeframe: Day 1 and End of cycle visit (Day 17) for Cycle 1-4 and Day 6-10 for Cycle 1
Summary of vital sign-heart rate (HR)
Timeframe: Day 1 and End of cycle visit (Day 17) for Cycle 1-4 and Day 6-10 for Cycle 1
Summary of vital sign respiration rate (RR)
Timeframe: Day 1 and End of cycle visit (Day 17) for Cycle 1-4 and Day 6-10 for Cycle 1
Number of participants with abnormal electrocardiogram (ECG) findings defined by clinical significance
Timeframe: Day 6-10, End of cycle (for cycle 1) and at follow-up 3-month
Interventions:
Enrollment:
1933
Primary completion date:
2007-29-08
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Herrstedt J, Apornwirat W, Shaharyar A, Aziz Z, Roila F, Van Belle S, Russo MW, Levin J, Ranganathan S, Guckert M, Grunberg SM. Phase III trial of casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy. 2009;27(32): 5363-9.
Medical condition
Nausea and Vomiting, Chemotherapy-Induced
Product
casopitant, ondansetron
Collaborators
Not applicable
Study date(s)
July 2006 to August 2007
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Inclusion criteria:
- A subject will be considered eligible for inclusion in this study only if all of the following criteria apply:
Inclusion and exclusion criteria
Inclusion criteria:
- Inclusion criteria:
- A subject will be considered eligible for inclusion in this 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 their first course of an anthracycline and cyclophosphamide containing moderately emetogenic chemotherapy regimen for the treatment of a solid malignant tumor as outlined in Section 8.1.1.
- Has an ECOG performance status of 0, 1, or 2.
- Hematologic and metabolic status must be adequate for receiving a moderately emetogenic regimen and meet 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 ULN ·Liver enzymes must be below the following limits: o Without known liver metastases: Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal. o 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: a.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) b.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 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. Exclusion criteria:
- Has previously received cytotoxic chemotherapy. A history of previous biological or hormonal therapy will be permitted.
- Is a female subject who is pregnant or lactating.
- Has received radiation therapy to the brain, abdomen, or pelvis in the ten days prior to the first dose of study medication or casopitant investigational product and/or will receive radiation therapy to the brain, abdomen, or the pelvis in the six days following the first dose of study medication (ZOFRAN and dexamethasone) or casopitant investigational product.
- Is scheduled to receive taxane therapy during cycle 1. Note that subjects will be permitted to receive taxane therapy in conjunction with one of the allowed MEC regimens during subsequent cycles.
- 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 casopitant investigational product.
- Has a known central nervous system primary or metastatic malignancy, unless successfully treated with excision or radiation and has been medically stable for at least 1 week prior to receiving the first dose of study medication or casopitant investigational product.
- 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.
- Received an investigational drug in the previous 30 days or is scheduled to receive any investigational drug other than casopitant during the study period.
- Has taken/received any medication of moderate or high emetogenic potential within the 48 hours prior to the first dose of study medication or casopitant investigational product. Opioid narcotics for cancer pain will be permitted if the subject has been on a stable dose 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 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 casopitant 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 therapy during subsequent cycles) ·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 during cycle 2-4 ·domperidone ·cannabinoids ·mirtazpine ·olanzapine
- Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 for a specified period prior to administration of casopitant investigational product (see Section 8.2.1 “Inhibitors of CYP3A4 and CYP3A5”)
- Has taken/received inducers of CYP3A4 and CYP3A5 within fourteen days prior to the administration of casopitant investigational product. (see Section 8.2.2 “Inducers of CYP3A4 and CYP3A5”)
- 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 (See Section 8.2.3 “Substrates for CYP2C8” and Section 8.4 “Necessary Caution with CYP2C8 Substrates”).
- Is currently taking or plans to take the any of the following CYP3A4 substrates: astemizole, cisapride, pimozide, terfenadine.
Trial location(s)
Location
GSK Investigational Site
Galesburg, Illinois, United States, 61401
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50677
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Sumter, South Carolina, United States, 29150
Status
Study Complete
Showing 1 - 6 of 234 Results
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2007-29-08
Actual study completion date
2007-29-08
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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