A Study of the Drug Casopitant for the Prevention of Nausea Caused By Cisplatin-Based Highly Emetogenic Chemotherapy
- Conditions
- Nausea and Vomiting, Chemotherapy-Induced
- Registration Number
- NCT00431236
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
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.
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 810
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Number of participants who achieved complete response Up to 120 hours of cycle 1 of HEC Complete response was defined as no vomiting/retching and no rescue therapy) over the first 120 hours following the initiation of their first cycle of a cisplatin-based HEC regimen. Vomiting was defined as the forceful expulsion of gastrointestinal contents through the mouth or nose. Retching was defined as the labored, spasmodic, rhythmic contraction of the respiratory and abdominal muscles in an attempt to vomit, that was not productive of gastrointestinal contents (also known as "dry heaves").
- Secondary Outcome Measures
Name Time Method Number of participants who use of anti-emetic rescue medication Up to 120 hours of each HEC cycle (up to 24 months) Anti-emetic rescue medication was defined as any medication, other than the protocol prescribed agents, given specifically for the treatment or prophylaxis of nausea and/or emesis during the 120 hour assessment phase of each study cycle. The time to the first anti-emetic rescue medication was defined as the length of time from initiation of HEC until the time of first use of anti-emetic rescue medication.
The willingness of participant to use the same treatment during future chemotherapy, as assessed by the participant willingness questionnaire Up to 120 hours of each HEC cycle (up to 24 months) A participant willingness questionnaire was included in the participants diary card. Participants completed this assessment on Day 6 - 10. Participants were asked to rate overall willingness to use study medications in preventing chemotherapy induced nausea and vomiting, using the 5-point scale: 1: definitely would be willing; 2: probably would be willing; 3: not certain; 4: probably would not be willing and 5: definitely would not be willing.
Number of participants who achieved complete response during the acute (0-24 hours) and the delayed (24-120 hours) phase following the first cycle of HEC Up to 120 hours of cycle 1 of HEC Complete response was defined as no vomiting/retching and no rescue therapy over the first 120 hours following the initiation of their first cycle of a cisplatin-based HEC regimen. Vomiting was defined as the forceful expulsion of gastrointestinal contents through the mouth or nose. Retching was defined as the labored, spasmodic, rhythmic contraction of the respiratory and abdominal muscles in an attempt to vomit, that was not productive of gastrointestinal contents (also known as "dry heaves").
Percentage of participants with impact on daily life activities for the first 120 hours following the first cycle of chemotherapy as assessed by the FLIE questionnaire-interpretation Up to 120 hours of each HEC cycle (up to 24 months) The FLIE was a self-administered questionnaire consisting of 18 items indicating impact of nausea and vomiting on daily activities: physical, social and emotional function, and the ability to enjoy meals. Questions are divided into two domains: nausea questions 1-9; vomiting questions 10-18. Each item was scored on a VAS from 1: not at all to 7: a great deal. Higher scores indicate less impairment on daily life as a result of nausea or vomiting. No impact on daily life was defined as an average item score of \>6 on the 7-point scale. The total score for no impact of chemotherapy induced nausea and vomiting (CINV) daily life, defined as a FLIE total score of \>108 (range: 18-126). The same method was applied to vomiting and nausea subscores: no impact of vomiting (nausea) on daily life was defined as a FLIE total score of \>54 (range: 9-63). The FLIE total score, as well as the vomiting and nausea subscores, for each treatment arm was calculated at Baseline and Day 6-10.
Summary of mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) Up to end of cycle (approximately 28 days per cycle); maximum up to 24 months It was assessed on Day 1, during day 6-10 and end of cycle in cycle 1 while on Day 1 and end of cycle in subsequent cycles 2 to 6. Summary of mean SBP and DBP is presented.
Maximum nausea score (to assess the severity of nausea), as assessed by a visual analogue scale (VAS) Up to 120 hours of each HEC cycle (up to 24 months) Nausea was defined as a subjectively unpleasant sensation associated with the awareness of the urge to vomit; the desire to vomit without the presence of expulsive muscular movements. The participants were asked to rate the level of nausea he/she has experienced over the previous 24 hours for a period of 120 hours on a 100-point VAS scale (millimeters \[mm\]) where, 0: no nausea and 100: nausea as bad as it could be. Higher score indicates more severity. The maximum nausea score (to assess the severity of nausea) was assessed by a VAS during the acute (0-24 hour), delayed (24-120 hour) and overall (0-120 hour) phase.
Number of participants with first emetic event Up to 120 hours of each HEC cycle (up to 24 months) Vomiting was defined as the forceful expulsion of gastrointestinal contents through the mouth or nose and retching was defined as the labored, spasmodic, rhythmic contraction of the respiratory and abdominal muscles in an attempt to vomit, that is not productive of gastrointestinal contents (also known as "dry heaves"). The time to first emetic event was defined as the length of time from initiation of HEC until the time of the first emetic event (example: retch/vomiting).
Number of participants who reported significant nausea (>=25 mm on the VAS) Up to 120 hours of cycle 1 of HEC Nausea was defined as a subjectively unpleasant sensation associated with the awareness of the urge to vomit; the desire to vomit without the presence of expulsive muscular movements. The participants were asked to rate the level of nausea he/she has experienced over the previous 24 hours for a period of 120 hours on a 100-point VAS scale (mm) where, 0: no nausea and 100: nausea as bad as it could be. Higher score indicates more severity. The maximum nausea score (to assess the severity of nausea) was assessed by a VAS during the acute (0-24 hour), delayed (24-120 hour) and overall (0-120 hour) phase.
Number of participants who achieved a complete response during the overall (0-120 hours) phase following subsequent cycles of HEC Up to 120 hours of cycle of HEC 2 to 6 Complete response was defined as no vomiting/retching and no rescue therapy over the first 120 hours following the initiation of their first cycle of a cisplatin-based HEC regimen. Vomiting was defined as the forceful expulsion of gastrointestinal contents through the mouth or nose. Retching was defined as the labored, spasmodic, rhythmic contraction of the respiratory and abdominal muscles in an attempt to vomit, that was not productive of gastrointestinal contents (also known as "dry heaves").
Number of participants who received anti-emetic rescue medication Up to 120 hours of cycle 1 of HEC Anti-emetic rescue medication was defined as any medication, other than the protocol prescribed agents, given specifically for the treatment or prophylaxis of nausea and/or emesis during the 120 hour assessment phase of each study cycle. The time to the first anti-emetic rescue medication was defined as the length of time from initiation of HEC until the time of first use of anti-emetic rescue medication. If no event had occurred at the end of the 120 hour time period, then the observation was censored for the purpose of this analysis.
Number of participants who vomited/retched Up to 120 hours of cycle 1 of HEC The forceful expulsion of gastrointestinal contents through the mouth or nose. The laboured, spasmodic, rhythmic contraction of the respiratory and abdominal muscles in an attempt to vomit, that was not productive of gastrointestinal contents (also known as "dry heaves"). It was assessed during the acute (0-24 hour), delayed (24-120 hour) and overall (0-120 hour) phase. The odds ratio indicated a reduction in the likelihood of vomiting in the single dose oral group and in the 3-Day IV/oral group compared with the control group.
Number of participants who reported nausea (>=5 mm on the VAS) Up to 120 hours of cycle 1 of HEC Nausea was defined as a subjectively unpleasant sensation associated with the awareness of the urge to vomit; the desire to vomit without the presence of expulsive muscular movements. The participants were asked to rate the level of nausea he/she has experienced over the previous 24 hours for a period of 120 hours on a 100-point VAS scale (mm) where, 0: no nausea and 100: nausea as bad as it could be. Higher score indicates more severity. The maximum nausea score (to assess the severity of nausea) was assessed by a VAS during the acute (0-24 hour), delayed (24-120 hour) and overall (0-120 hour) phase.
Number of participants who achieved total control, defined as no vomiting/retching, no nausea and no rescue medication Up to 120 hours of each HEC cycle (up to 24 months) Total control was defined as no vomiting, no retching, no rescue therapy and no nausea (\<5 mm on VAS). It was assessed during the acute (0-24 hour), delayed (24-120 hour) and overall (0-120 hour) phase.
Summary of abnormal electrocardiogram findings Up to end of cycle (approximately 28 days per cycle); maximum up to 24 months It was assessed on Day 1, during day 6-10 and end of cycle. Electrocardiogram data clinically significant change from Baseline (worse, improved and no change) is presented.
Summary of mean heart rate Up to end of cycle (approximately 28 days per cycle); maximum up to 24 months It was assessed on Day 1, during day 6-10 and end of cycle in cycle 1 while on Day 1and end of cycle in subsequent cycles 2 to 6. Summary of mean heart rate is presented.
Number of participants who achieved complete protection, defined as no vomiting/retching, no significant nausea and no rescue medication Up to 120 hours of cycle 1 of HEC Complete protection was defined as no vomiting/retching, no rescue therapy and no significant nausea (\<25 mm on VAS). It was assessed during the acute (0-24 hour), delayed (24-120 hour) and overall (0-120 hour) phase.
Participant satisfaction with the prophylactic anti-emetic regimens, as assessed by the participant satisfaction questionnaire Up to 120 hours of each HEC cycle (up to 24 months) A participant satisfaction questionnaire was included in the participants diary card. At Day 6-10 of cycle 1, participants were asked to rate overall satisfaction with study medications in preventing chemotherapy induced nausea and vomiting, using the 5-point scale: 1: very satisfied; 2: somewhat satisfied; 3: neither satisfied nor dissatisfied; 4: somewhat dissatisfied and 5: very dissatisfied, where higher score indicates greater dissatisfaction.
Number of participants with nausea as assessed by a categorical scale, over the first 120 hours following HEC Up to 120 hours of each HEC cycle (up to 24 months) Nausea was defined as a subjectively unpleasant sensation associated with the awareness of the urge to vomit; the desire to vomit without the presence of expulsive muscular movements. The categorical scale assessed the participant's severity of his/her nausea using the descriptions; none: no nausea, mild: queasiness/upset stomach that was manageable and minimally (if at all) affects daily activities; moderate: increased queasiness, sometimes with the feeling of having to vomit/throw up (but not vomiting), that has significant negative effect on the daily activities (for example, being unable to work, eat and drink, prepare food, care for children or others) and severe: feeling sick and vomiting or feeling like you are going to vomit and unable to perform most daily activities.
Number of participants with adverse events (AE) and serious adverse events (SAE) Up to 24 month after last dose of investigational product An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Summary of mean respiratory rate Up to end of cycle (approximately 28 days per cycle); maximum up to 24 months It was assessed on Day 1, during day 6-10 and end of cycle in cycle 1 while on Day 1and end of cycle in subsequent cycles 2 to 6. Summary of mean respiratory rate is presented.
The impact on participants daily life activities for the first 120 hours following the first cycle of chemotherapy as assessed by the Functional Living Index-Emesis (FLIE) questionnaire-Score Up to 120 hours of each HEC cycle (up to 24 months) The FLIE was a self-administered questionnaire consisting of 18 items indicating impact of nausea and vomiting on daily activities: physical, social and emotional function, and the ability to enjoy meals. Questions are divided into two domains: nausea 1-9; vomiting 10-18. Each item was scored on a VAS from 1: not at all to 7: a great deal; higher score indicates more severity. The initial score for each question was calculated by measuring the distance from the left hand end to the point where the participant had placed the mark. For questions 1, 2, 4, 5, 7-10, 12-14, 16 and 17, the final score: subtracting the initial score from 100 and for questions 3, 6, 11, 15 and 18, final score was the one provided in the dataset. The score for the nausea/vomiting domain was the sum of the individual scores divided by the number actually answered multiplied by 9. This sum was then multiplied by 0.06 and 9 added. The score ranged from 9-63 for each nausea and vomiting and sum both is provided.
Number of participants with abnormalities of Grade 3 and 4 in laboratory parameters (clinical chemistry and hematology) Up to end of cycle (approximately 28 days per cycle); maximum up to 24 months Grade shifts from Baseline were assessed as shift from any Grade to Grade 3 or Grade 4 in any cycle. Toxicities were graded according to the National Cancer Institute common toxicity criteria for adverse events (NCI-CTCAE), version 3.0. Grade refers to the severity of the toxicity. The NCI-CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. It was assessed on Day 1, during day 6-10 and end of cycle. Clinical chemistry parameters assessed included: alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, creatinine, blood urea nitrogen (BUN), chloride, glucose, potassium, sodium and urea. Hematology parameters assessed included: hemoglobin, hematocrit, total neutrophils, platelets and white blood cells (WBC).
Trial Locations
- Locations (1)
GSK Investigational Site
🇺🇦Uzhgorod, Ukraine