Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 4 of 12 for:    rolapitant

Ph3 Safety/Efficacy Study of Rolapitant for the Prevention of CINV in Subjects Receiving Highly Emetogenic Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01499849
Recruitment Status : Completed
First Posted : December 26, 2011
Results First Posted : November 4, 2015
Last Update Posted : May 19, 2016
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Chemotherapy-induced Nausea and Vomiting
Interventions Drug: Rolapitant
Drug: Granisetron
Drug: dexamethasone
Drug: Placebo
Enrollment 532
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rolapitant + Granisetron + Dexamethasone Placebo + Granisetron + Dexamethasone
Hide Arm/Group Description
  • Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
  • Matching placebo 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
Period Title: Overall Study
Started 266 [1] 266
Completed 42 [2] 40
Not Completed 224 226
Reason Not Completed
Adverse Event             28             32
Chemo completed or Change in Therapy             70             67
Withdrawal by Subject             43             43
Death             5             7
Disease Progression             11             10
Protocol Violation             11             11
Physician Decision             20             19
Lack of Efficacy             3             4
Lost to Follow-up             6             3
Other Reasons             27             30
[1]
Number of randomized patients
[2]
Number of patients who completed 6 cycles
Arm/Group Title Rolapitant + Granisetron + Dexamethasone Placebo + Granisetron + Dexamethasone Total
Hide Arm/Group Description
  • Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
  • Matching placebo 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
Total of all reporting groups
Overall Number of Baseline Participants 264 262 526
Hide Baseline Analysis Population Description
Overall Number of Baseline Participants only included the Modified Intent to Treat (MITT) population: 266 subjects were randomized to Rolapitant and 266 were randomized to control; 264 of those randomized to Rolapitant received study drug in Cycle 1; 262 of those who were randomized to control received study drug in Cycle 1.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 264 participants 262 participants 526 participants
57.0  (10.08) 57.7  (11.15) 57.3  (10.62)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 264 participants 262 participants 526 participants
Female
110
  41.7%
112
  42.7%
222
  42.2%
Male
154
  58.3%
150
  57.3%
304
  57.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 264 participants 262 participants 526 participants
Hispanic or Latino
33
  12.5%
34
  13.0%
67
  12.7%
Not Hispanic or Latino
231
  87.5%
228
  87.0%
459
  87.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 264 participants 262 participants 526 participants
American Indian or Alaska Native
2
   0.8%
0
   0.0%
2
   0.4%
Asian
61
  23.1%
56
  21.4%
117
  22.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   0.8%
3
   1.1%
5
   1.0%
White
178
  67.4%
179
  68.3%
357
  67.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
21
   8.0%
24
   9.2%
45
   8.6%
1.Primary Outcome
Title No Emetic Episodes and No Rescue Medication
Hide Description The primary objective of this study is to determine whether administration of rolapitant with granisetron and dexamethasone improves CINV in the delayed phase (>24 to 120 hours) of CINV compared with administration of placebo with granisetron and dexamethasone in subjects receiving HEC. The primary outcome will be based on complete response (defined as no emetic episodes and no rescue medication) in the delayed phase (>24 to 120 hours).
Time Frame >24 to 120 hours post chemotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
MITT
Arm/Group Title Rolapitant + Granisetron + Dexamethasone Placebo + Granisetron + Dexamethasone
Hide Arm/Group Description:
  • Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
  • Matching placebo 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
Overall Number of Participants Analyzed 264 262
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
72.7
(66.9 to 78.0)
58.4
(52.2 to 64.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rolapitant + Granisetron + Dexamethasone, Placebo + Granisetron + Dexamethasone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments To control for multiplicity, analyses were performed hierarchically. For the CR delayed the threshold for statistical significance was 0.05; no further adjustment for multiplicity were required for the primary endpoint.
Method Cochran-Mantel-Haenszel
Comments Cochran Mantel Haenszel (CMH) test was stratified by sex. Missing data were imputed as treatment failures.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
1.3 to 2.7
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Acute Phase Response
Hide Description To determine the effect of rolapitant on complete response rates in the acute (0 to 24 hours)phase of CINV
Time Frame 0 to 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
MITT
Arm/Group Title Rolapitant + Granisetron + Dexamethasone Placebo + Granisetron + Dexamethasone
Hide Arm/Group Description:
  • Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
  • Matching placebo 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
Overall Number of Participants Analyzed 264 262
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
83.7
(78.7 to 88.0)
73.7
(67.9 to 78.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rolapitant + Granisetron + Dexamethasone, Placebo + Granisetron + Dexamethasone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments To control for multiplicity, analyses were performed hierarchically. CR-acute was tested only if the result for the primary endpoint, CR delayed, was statistically significant.
Method Cochran-Mantel-Haenszel
Comments Cochran Mantel Haenszel (CMH) test was stratified by sex. Missing data were imputed as treatment failures.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
1.2 to 2.8
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Overall Response Rate
Hide Description To determine the effect of rolapitant on complete response rates in the overall (0 to 120 hours) phase of CINV.
Time Frame 0 to 120 hours
Hide Outcome Measure Data
Hide Analysis Population Description
MITT
Arm/Group Title Rolapitant + Granisetron + Dexamethasone Placebo + Granisetron + Dexamethasone
Hide Arm/Group Description:
  • Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
  • Matching placebo 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
Overall Number of Participants Analyzed 264 262
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
70.1
(64.2 to 75.5)
56.5
(50.2 to 62.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rolapitant + Granisetron + Dexamethasone, Placebo + Granisetron + Dexamethasone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments To control for multiplicity, analyses were performed hierarchically. CR overall was tested only if both CR delayed and CR acute were statistically significant.
Method Cochran-Mantel-Haenszel
Comments Cochran Mantel Haenszel (CMH) test was stratified by sex. Missing data were imputed as treatment failures.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
1.3 to 2.6
Estimation Comments [Not Specified]
Time Frame Up to 6 cycles of treatment (median number cycles=2; median duration of each cycle = 21-22 days)
Adverse Event Reporting Description Safety analysis was based on actual treatment received in Cycle 1. 266 subjects were randomized to Rolapitant, among which 263 received Rolapitant in Cycle 1, hence Safety=263 for Rolapitant. 266 subjects were randomized to control, among which 263 received control in Cycle 1 (There was an error in treatment received), hence Safety=263 for control.
 
Arm/Group Title Rolapitant + Granisetron + Dexamethasone Placebo + Granisetron + Dexamethasone
Hide Arm/Group Description
  • Oral dose of rolapitant 180 mg (equivalent to 200 mg rolapitant hydrochloride monohydrate) 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
  • Matching placebo 1-2 h before administration of chemotherapy
  • Granisetron (10 μg/kg intravenously) about 30 min before chemotherapy
  • Dexamethasone (20 mg orally) about 30 min before chemotherapy, and dexamethasone 8 mg orally twice daily on days 2-4
All-Cause Mortality
Rolapitant + Granisetron + Dexamethasone Placebo + Granisetron + Dexamethasone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Rolapitant + Granisetron + Dexamethasone Placebo + Granisetron + Dexamethasone
Affected / at Risk (%) Affected / at Risk (%)
Total   37/263 (14.07%)   54/263 (20.53%) 
Blood and lymphatic system disorders     
Agranulocytosis  1  0/263 (0.00%)  1/263 (0.38%) 
Febrile Neutropenia * 1  3/263 (1.14%)  2/263 (0.76%) 
Neutropenia * 1  0/263 (0.00%)  2/263 (0.76%) 
Pancytopenia * 1  1/263 (0.38%)  0/263 (0.00%) 
Cardiac disorders     
Atrial Fibrillation * 1  1/263 (0.38%)  0/263 (0.00%) 
Cardiac Failure * 1  1/263 (0.38%)  0/263 (0.00%) 
Cardio-Respiratory Arrest * 1  0/263 (0.00%)  1/263 (0.38%) 
Cardiomyopathy * 1  1/263 (0.38%)  0/263 (0.00%) 
Supraventricular Tachycardia * 1  0/263 (0.00%)  1/263 (0.38%) 
Gastrointestinal disorders     
Abdominal Pain  1  0/263 (0.00%)  1/263 (0.38%) 
Gastric Ulcer Haemorrhage * 1  0/263 (0.00%)  1/263 (0.38%) 
Gastric Ulcer Perforation * 1  0/263 (0.00%)  1/263 (0.38%) 
Gastrointestinal Disorder * 1  0/263 (0.00%)  1/263 (0.38%) 
Ileus * 1  1/263 (0.38%)  1/263 (0.38%) 
Impaired Gastric Empyting * 1  1/263 (0.38%)  0/263 (0.00%) 
Nausea * 1  0/263 (0.00%)  2/263 (0.76%) 
Odynophagia  1  0/263 (0.00%)  1/263 (0.38%) 
Small Intestinal Perforation * 1  1/263 (0.38%)  0/263 (0.00%) 
Upper Gastrointestinal Haemorrhage * 1  1/263 (0.38%)  0/263 (0.00%) 
Vomiting * 1  0/263 (0.00%)  5/263 (1.90%) 
General disorders     
Asthenia * 1  0/263 (0.00%)  1/263 (0.38%) 
Death * 1  0/263 (0.00%)  3/263 (1.14%) 
Disease Progression * 1  1/263 (0.38%)  2/263 (0.76%) 
Fatigue * 1  0/263 (0.00%)  1/263 (0.38%) 
General Physical Health Deterioration * 1  1/263 (0.38%)  0/263 (0.00%) 
Malaise * 1  1/263 (0.38%)  1/263 (0.38%) 
Multi-Organ Failure * 1  0/263 (0.00%)  2/263 (0.76%) 
Non-Cardiac Chest Pain * 1  1/263 (0.38%)  0/263 (0.00%) 
Sudden Death  1  1/263 (0.38%)  0/263 (0.00%) 
Immune system disorders     
Anaphylactic Reaction * 1  0/263 (0.00%)  1/263 (0.38%) 
Infections and infestations     
Bacterial Sepsis * 1  0/263 (0.00%)  1/263 (0.38%) 
Bronchitis Bacterial * 1  1/263 (0.38%)  0/263 (0.00%) 
Encephalitis Herpes * 1  0/263 (0.00%)  1/263 (0.38%) 
Endocarditis * 1  1/263 (0.38%)  0/263 (0.00%) 
Gastroenteritis viral * 1  0/263 (0.00%)  1/263 (0.38%) 
Infective Exacerabation of Bronchiectasis * 1  0/263 (0.00%)  1/263 (0.38%) 
Lung Abscess * 1  0/263 (0.00%)  1/263 (0.38%) 
Neutropenic Sepsis * 1  1/263 (0.38%)  0/263 (0.00%) 
Pneumonia * 1  5/263 (1.90%)  1/263 (0.38%) 
Pseudomonal sepsis * 1  1/263 (0.38%)  0/263 (0.00%) 
Pyelonephritis  1  0/263 (0.00%)  1/263 (0.38%) 
Sepsis * 1  0/263 (0.00%)  2/263 (0.76%) 
Septic Shock * 1  1/263 (0.38%)  0/263 (0.00%) 
Metabolism and nutrition disorders     
Dehydration * 1  2/263 (0.76%)  5/263 (1.90%) 
Diabetes Mellitus * 1  1/263 (0.38%)  0/263 (0.00%) 
Hypokalemia * 1  0/263 (0.00%)  1/263 (0.38%) 
Malnutrition * 1  1/263 (0.38%)  0/263 (0.00%) 
Musculoskeletal and connective tissue disorders     
Hypercreatinaemia * 1  0/263 (0.00%)  1/263 (0.38%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bronchial Carcinoma * 1  0/263 (0.00%)  1/263 (0.38%) 
Gastrointestinal Stromal Cancer * 1  0/263 (0.00%)  1/263 (0.38%) 
Neoplasm Progression * 1  1/263 (0.38%)  0/263 (0.00%) 
Nervous system disorders     
Cerebrovascular Accident * 1  2/263 (0.76%)  1/263 (0.38%) 
Convulsion * 1  1/263 (0.38%)  1/263 (0.38%) 
Ischaemic Stroke * 1  1/263 (0.38%)  2/263 (0.76%) 
Loss of Consciousness * 1  0/263 (0.00%)  1/263 (0.38%) 
Syncope * 1  0/263 (0.00%)  1/263 (0.38%) 
Transient Ischaemic Attack * 1  0/263 (0.00%)  1/263 (0.38%) 
Renal and urinary disorders     
Renal Failure Acute * 1  2/263 (0.76%)  3/263 (1.14%) 
Respiratory, thoracic and mediastinal disorders     
Acute Respiratory Failure * 1  0/263 (0.00%)  1/263 (0.38%) 
Bronchopleural Fistula * 1  1/263 (0.38%)  0/263 (0.00%) 
Hydropneumothorax * 1  0/263 (0.00%)  1/263 (0.38%) 
Pleural Effusion * 1  1/263 (0.38%)  0/263 (0.00%) 
Pneumonitis * 1  1/263 (0.38%)  0/263 (0.00%) 
Pneumothorax * 1  0/263 (0.00%)  1/263 (0.38%) 
Pulmonary Embolism * 1  2/263 (0.76%)  4/263 (1.52%) 
Respiratory Distress * 1  0/263 (0.00%)  1/263 (0.38%) 
Respiratory Failure * 1  2/263 (0.76%)  0/263 (0.00%) 
Vascular disorders     
Deep Vein Thrombosis * 1  1/263 (0.38%)  0/263 (0.00%) 
Embolism * 1  0/263 (0.00%)  1/263 (0.38%) 
Hypotension * 1  0/263 (0.00%)  1/263 (0.38%) 
Orthostatic Hypotension * 1  0/263 (0.00%)  1/263 (0.38%) 
Superior Vena Cava Syndrome * 1  0/263 (0.00%)  1/263 (0.38%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rolapitant + Granisetron + Dexamethasone Placebo + Granisetron + Dexamethasone
Affected / at Risk (%) Affected / at Risk (%)
Total   187/263 (71.10%)   198/263 (75.29%) 
Blood and lymphatic system disorders     
Anaemia * 1  28/263 (10.65%)  32/263 (12.17%) 
Leukopenia * 1  18/263 (6.84%)  14/263 (5.32%) 
Neutropenia * 1  33/263 (12.55%)  23/263 (8.75%) 
Thrombocytopenia * 1  16/263 (6.08%)  12/263 (4.56%) 
Gastrointestinal disorders     
Constipation * 1  26/263 (9.89%)  29/263 (11.03%) 
Diarrhoea * 1  20/263 (7.60%)  18/263 (6.84%) 
Dyspepsia * 1  18/263 (6.84%)  8/263 (3.04%) 
Nausea * 1  24/263 (9.13%)  35/263 (13.31%) 
Stomatitis * 1  16/263 (6.08%)  14/263 (5.32%) 
vomiting * 1  9/263 (3.42%)  22/263 (8.37%) 
General disorders     
Asthenia * 1  35/263 (13.31%)  40/263 (15.21%) 
Fatigue * 1  36/263 (13.69%)  30/263 (11.41%) 
Mucosal Inflammation * 1  17/263 (6.46%)  19/263 (7.22%) 
Metabolism and nutrition disorders     
Decreased Appetite * 1  30/263 (11.41%)  36/263 (13.69%) 
Dehydration * 1  13/263 (4.94%)  15/263 (5.70%) 
Respiratory, thoracic and mediastinal disorders     
Hiccups * 1  16/263 (6.08%)  8/263 (3.04%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  22/263 (8.37%)  23/263 (8.75%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Martin Huber, M.D., Senior Vice President and Chief Medical Officer
Organization: Tesaro
Phone: 781.257.2536
EMail: mhuber@tesarobio.com
Layout table for additonal information
Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT01499849    
Other Study ID Numbers: TS-P04832
First Submitted: December 20, 2011
First Posted: December 26, 2011
Results First Submitted: October 2, 2015
Results First Posted: November 4, 2015
Last Update Posted: May 19, 2016