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

• Sponsor: Tesaro, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01499849
• Collaborator: (none)
• Enrollment: 532
• Location: 1
• Arms: 2
• Duration (Months): 26.9
• Patients Per Site Per Month: 19.7

Study Details

Study Description

Brief Summary

This is a Phase 3, multicenter, randomized, parallel-group, double-blind, active-controlled study of rolapitant in subjects receiving HEC. Rolapitant or placebo will be administered prior to initiation of chemotherapy on Day 1 with granisetron and dexamethasone. Subjects will record all events of emesis and use of rescue medication for established nausea and/or vomiting, and will indicate the severity of nausea they experienced in each of the previous 24 hours in the Nausea and Vomiting (NV) Subject Diary prior to HEC administration through Day 6 of Cycle 1. Health-related quality of life will be measured by the FLIE Questionnaire on Day 6 of Cycle 1. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.

All subjects are expected to complete Cycle 1 and will have the option of participating in up to five additional cycles.

Condition or Disease	Intervention/Treatment	Phase
Chemotherapy-induced Nausea and Vomiting	Drug: Rolapitant; Drug: Granisetron; Drug: dexamethasone; Drug: Placebo	Phase 3

Detailed Description

This is a Phase 3, multicenter, randomized, parallel-group, double-blind, active-controlled study of rolapitant in subjects receiving HEC (≥60 mg/m2 of cisplatin-based chemotherapy). Study drug will be administered 1 - 2 hours prior to initiation of chemotherapy on Day 1. Granisetron and dexamethasone will be administered approximately 30 minutes before initiation of chemotherapy on Day 1,except in patients receiving taxanes as part of cisplatin-based chemotherapy. Subjects will record all events of emesis and use of rescue medication for established nausea and/or vomiting and will indicate the severity of nausea they experienced in each of the previous 24 hours in the NV Subject Diary prior to HEC administration through Day 6 in Cycle 1. Dexamethasone 8 mg twice daily (part of study regimen) on Days 2 through 4 is NOT considered rescue therapy. Health-related quality of life will be measured by the FLIE Questionnaire on Day 6 of Cycle 1. Safety and tolerability will be assessed by clinical review of AEs, physical examinations including complete neurological assessment, vital signs,electrocardiograms (ECGs), and safety laboratory values including BUN andcreatinine. All subjects are expected to complete Cycle 1 and will have the option of participating in up to five additional cycles. The study will investigate the efficacy of rolapitant for the treatment of CINV during an initial chemotherapy cycle (Cycle 1).

Safety analyses will include data from Cycle 1 and from subsequent cycles. At the Screening Visit, blood samples may be collected and stored in this study and maybe analyzed for future biomarker research related to safety and efficacy. Analysis of these samples may include DNA, RNA, or protein markers. The biomarker blood samples will be stored for up to 2 years post study completion. In addition, PK samples will be collected from subjects enrolled in selected sites.

Study Design

• Study Type: Interventional
• Actual Enrollment: 532 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Phase 3, Multicenter, Randomized, Double Blind, Active-Controlled Study of the Safety & Efficacy of Rolapitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Subjects Receiving Highly Emetogenic Chemotherapy (HEC)
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rolapitant Day 1: Rolapitant (200 mg PO) + Granisetron (10 mcg/kg IV) + dexamethasone (20 mg PO) Days 2-4: Dexamethasone (8 mg PO) will be administered orally BID.	Drug: Rolapitant; (4 X 50 mg capsules) 200 mg PO; Other Names: Varubi ; Drug: Granisetron; 10 mcg/kg IV; Other Names: Kytril Granisol ; Drug: dexamethasone; 20 mg PO and 8 mg PO; Other Names: Decadron
Placebo Comparator: Placebo + Granisetron + Dexamethasone Day 1: Placebo + Granisetron (10 mcg/kg IV)+ dexamethasone (20 mg PO) Days 2-4: Dexamethasone (8 mg PO) will be administered orally BID.	Drug: Granisetron; 10 mcg/kg IV; Other Names: Kytril Granisol ; Drug: dexamethasone; 20 mg PO and 8 mg PO; Other Names: Decadron ; Drug: Placebo; (4 X 0 mg capsules) 0 mg PO; Other Names: Placebo to match Rolapitant

Outcome Measures

Primary Outcome Measures

1. No Emetic Episodes and No Rescue Medication [>24 to 120 hours post chemotherapy]

   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).

Secondary Outcome Measures

1. Acute Phase Response [0 to 24 hours]

   To determine the effect of rolapitant on complete response rates in the acute (0 to 24 hours)phase of CINV

2. Overall Response Rate [0 to 120 hours]

   To determine the effect of rolapitant on complete response rates in the overall (0 to 120 hours) phase of CINV.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years of age or older, of either gender, and of any race

• has never been treated with cisplatin and is to receive the first course of cisplatin-based chemotherapy (≥60 mg/m2)

• Karnofsky performance score of ≥60

• Predicted life expectancy of ≥4 months

• Adequate bone marrow, kidney, and liver function

Exclusion Criteria:

• Contraindication to cisplatin, granisetron, or dexamethasone

• Is pregnant or breast feeding

• Has previously received cisplatin or subject is planning to receive multiple days of cisplatin in a single cycle

• Has taken the following agents within the last 48 hours 5-HT3 antagonists,Phenothiazines,Benzamides,Domperidone,Cannabinoids,NK1 antagonist, Benzodiazepines

• Scheduled to receive any other chemotherapeutic agent with an emetogenicity level of 4 or above (Hesketh Scale) from Day 2 through Day 6, except on Day 1.

• Scheduled to receive any radiation therapy to the abdomen or pelvis from Day -5 through Day 6

• Has received systemic corticosteroids or sedative antihistamines within 72 hours of Day 1 of the study except as premedication for chemotherapy (e.g., taxanes, pemetrexed)

• symptomatic primary or metastatic CNS disease.

• Has ongoing vomiting, retching, clinically significant nausea caused by any etiology, or has a history of anticipatory nausea and vomiting.

• Has vomited and/or has had dry heaves/retching within 24 hours prior to the start of cisplatin-based chemotherapy on Day 1 in Cycle 1.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	TESARO Inc	Waltham	Massachusetts	United States	02451

Sponsors and Collaborators

• Tesaro, Inc.

Investigators

• Study Director: Dennis Vargo, MD, Tesaro, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tesaro, Inc.
• ClinicalTrials.gov Identifier: NCT01499849
• Other Study ID Numbers: TS-P04832
• First Posted: Dec 26, 2011
• Last Update Posted: May 19, 2016
• Last Verified: Oct 1, 2012

• Keywords provided by Tesaro, Inc.: Rolapitant; Nausea; Vomiting; CINV; Chemotherapy
• Additional relevant MeSH terms: Nausea; Vomiting; Dexamethasone; Granisetron; Rolapitant

Study Results

Participant Flow

Arm/Group Title	Rolapitant + Granisetron + Dexamethasone	Placebo + Granisetron + Dexamethasone
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	266
COMPLETED	42	40
NOT COMPLETED	224	226

Baseline Characteristics

Arm/Group Title	Rolapitant + Granisetron + Dexamethasone	Placebo + Granisetron + Dexamethasone	Total
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 Participants	264	262	526
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.0 (10.08)	57.7 (11.15)	57.3 (10.62)
Sex: Female, Male (Count of Participants)
Female	110 41.7%	112 42.7%	222 42.2%
Male	154 58.3%	150 57.3%	304 57.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	33 12.5%	34 13%	67 12.7%
Not Hispanic or Latino	231 87.5%	228 87%	459 87.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.8%	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%
Black or African American	2 0.8%	3 1.1%	5 1%
White	178 67.4%	179 68.3%	357 67.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	21 8%	24 9.2%	45 8.6%

Outcome Measures

1. Primary Outcome

Title	No Emetic Episodes and No Rescue Medication
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

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	Rolapitant + Granisetron + Dexamethasone	Placebo + Granisetron + Dexamethasone
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
Measure Participants	264	262
Number (95% Confidence Interval) [percentage of participants]	72.7 27.5%	58.4 22.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rolapitant + Granisetron + Dexamethasone, Placebo + Granisetron + Dexamethasone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Acute Phase Response
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

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	Rolapitant + Granisetron + Dexamethasone	Placebo + Granisetron + Dexamethasone
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
Measure Participants	264	262
Number (95% Confidence Interval) [percentage of participants]	83.7 31.7%	73.7 28.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rolapitant + Granisetron + Dexamethasone, Placebo + Granisetron + Dexamethasone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Overall Response Rate
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

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	Rolapitant + Granisetron + Dexamethasone	Placebo + Granisetron + Dexamethasone
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
Measure Participants	264	262
Number (95% Confidence Interval) [percentage of participants]	70.1 26.6%	56.5 21.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rolapitant + Granisetron + Dexamethasone, Placebo + Granisetron + Dexamethasone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rolapitant + Granisetron + Dexamethasone		Placebo + Granisetron + Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/263 (14.1%)		54/263 (20.5%)
Blood and lymphatic system disorders
Agranulocytosis	0/263 (0%)		1/263 (0.4%)
Febrile Neutropenia	3/263 (1.1%)		2/263 (0.8%)
Neutropenia	0/263 (0%)		2/263 (0.8%)
Pancytopenia	1/263 (0.4%)		0/263 (0%)
Cardiac disorders
Atrial Fibrillation	1/263 (0.4%)		0/263 (0%)
Cardiac Failure	1/263 (0.4%)		0/263 (0%)
Cardio-Respiratory Arrest	0/263 (0%)		1/263 (0.4%)
Cardiomyopathy	1/263 (0.4%)		0/263 (0%)
Supraventricular Tachycardia	0/263 (0%)		1/263 (0.4%)
Gastrointestinal disorders
Abdominal Pain	0/263 (0%)		1/263 (0.4%)
Gastric Ulcer Haemorrhage	0/263 (0%)		1/263 (0.4%)
Gastric Ulcer Perforation	0/263 (0%)		1/263 (0.4%)
Gastrointestinal Disorder	0/263 (0%)		1/263 (0.4%)
Ileus	1/263 (0.4%)		1/263 (0.4%)
Impaired Gastric Empyting	1/263 (0.4%)		0/263 (0%)
Nausea	0/263 (0%)		2/263 (0.8%)
Odynophagia	0/263 (0%)		1/263 (0.4%)
Small Intestinal Perforation	1/263 (0.4%)		0/263 (0%)
Upper Gastrointestinal Haemorrhage	1/263 (0.4%)		0/263 (0%)
Vomiting	0/263 (0%)		5/263 (1.9%)
General disorders
Asthenia	0/263 (0%)		1/263 (0.4%)
Death	0/263 (0%)		3/263 (1.1%)
Disease Progression	1/263 (0.4%)		2/263 (0.8%)
Fatigue	0/263 (0%)		1/263 (0.4%)
General Physical Health Deterioration	1/263 (0.4%)		0/263 (0%)
Malaise	1/263 (0.4%)		1/263 (0.4%)
Multi-Organ Failure	0/263 (0%)		2/263 (0.8%)
Non-Cardiac Chest Pain	1/263 (0.4%)		0/263 (0%)
Sudden Death	1/263 (0.4%)		0/263 (0%)
Immune system disorders
Anaphylactic Reaction	0/263 (0%)		1/263 (0.4%)
Infections and infestations
Bacterial Sepsis	0/263 (0%)		1/263 (0.4%)
Bronchitis Bacterial	1/263 (0.4%)		0/263 (0%)
Encephalitis Herpes	0/263 (0%)		1/263 (0.4%)
Endocarditis	1/263 (0.4%)		0/263 (0%)
Gastroenteritis viral	0/263 (0%)		1/263 (0.4%)
Infective Exacerabation of Bronchiectasis	0/263 (0%)		1/263 (0.4%)
Lung Abscess	0/263 (0%)		1/263 (0.4%)
Neutropenic Sepsis	1/263 (0.4%)		0/263 (0%)
Pneumonia	5/263 (1.9%)		1/263 (0.4%)
Pseudomonal sepsis	1/263 (0.4%)		0/263 (0%)
Pyelonephritis	0/263 (0%)		1/263 (0.4%)
Sepsis	0/263 (0%)		2/263 (0.8%)
Septic Shock	1/263 (0.4%)		0/263 (0%)
Metabolism and nutrition disorders
Dehydration	2/263 (0.8%)		5/263 (1.9%)
Diabetes Mellitus	1/263 (0.4%)		0/263 (0%)
Hypokalemia	0/263 (0%)		1/263 (0.4%)
Malnutrition	1/263 (0.4%)		0/263 (0%)
Musculoskeletal and connective tissue disorders
Hypercreatinaemia	0/263 (0%)		1/263 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial Carcinoma	0/263 (0%)		1/263 (0.4%)
Gastrointestinal Stromal Cancer	0/263 (0%)		1/263 (0.4%)
Neoplasm Progression	1/263 (0.4%)		0/263 (0%)
Nervous system disorders
Cerebrovascular Accident	2/263 (0.8%)		1/263 (0.4%)
Convulsion	1/263 (0.4%)		1/263 (0.4%)
Ischaemic Stroke	1/263 (0.4%)		2/263 (0.8%)
Loss of Consciousness	0/263 (0%)		1/263 (0.4%)
Syncope	0/263 (0%)		1/263 (0.4%)
Transient Ischaemic Attack	0/263 (0%)		1/263 (0.4%)
Renal and urinary disorders
Renal Failure Acute	2/263 (0.8%)		3/263 (1.1%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	0/263 (0%)		1/263 (0.4%)
Bronchopleural Fistula	1/263 (0.4%)		0/263 (0%)
Hydropneumothorax	0/263 (0%)		1/263 (0.4%)
Pleural Effusion	1/263 (0.4%)		0/263 (0%)
Pneumonitis	1/263 (0.4%)		0/263 (0%)
Pneumothorax	0/263 (0%)		1/263 (0.4%)
Pulmonary Embolism	2/263 (0.8%)		4/263 (1.5%)
Respiratory Distress	0/263 (0%)		1/263 (0.4%)
Respiratory Failure	2/263 (0.8%)		0/263 (0%)
Vascular disorders
Deep Vein Thrombosis	1/263 (0.4%)		0/263 (0%)
Embolism	0/263 (0%)		1/263 (0.4%)
Hypotension	0/263 (0%)		1/263 (0.4%)
Orthostatic Hypotension	0/263 (0%)		1/263 (0.4%)
Superior Vena Cava Syndrome	0/263 (0%)		1/263 (0.4%)
Other (Not Including Serious) Adverse Events
	Rolapitant + Granisetron + Dexamethasone		Placebo + Granisetron + Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	187/263 (71.1%)		198/263 (75.3%)
Blood and lymphatic system disorders
Anaemia	28/263 (10.6%)		32/263 (12.2%)
Leukopenia	18/263 (6.8%)		14/263 (5.3%)
Neutropenia	33/263 (12.5%)		23/263 (8.7%)
Thrombocytopenia	16/263 (6.1%)		12/263 (4.6%)
Gastrointestinal disorders
Constipation	26/263 (9.9%)		29/263 (11%)
Diarrhoea	20/263 (7.6%)		18/263 (6.8%)
Dyspepsia	18/263 (6.8%)		8/263 (3%)
Nausea	24/263 (9.1%)		35/263 (13.3%)
Stomatitis	16/263 (6.1%)		14/263 (5.3%)
vomiting	9/263 (3.4%)		22/263 (8.4%)
General disorders
Asthenia	35/263 (13.3%)		40/263 (15.2%)
Fatigue	36/263 (13.7%)		30/263 (11.4%)
Mucosal Inflammation	17/263 (6.5%)		19/263 (7.2%)
Metabolism and nutrition disorders
Decreased Appetite	30/263 (11.4%)		36/263 (13.7%)
Dehydration	13/263 (4.9%)		15/263 (5.7%)
Respiratory, thoracic and mediastinal disorders
Hiccups	16/263 (6.1%)		8/263 (3%)
Skin and subcutaneous tissue disorders
Alopecia	22/263 (8.4%)		23/263 (8.7%)

Limitations/Caveats

[Not Specified]

More Information

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.