PIONEER: Phase III Study Comparing the Efficacy and Safety of EP2006 and Filgrastim

• Sponsor: Sandoz (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01519700
• Collaborator: (none)
• Enrollment: 218
• Locations: 26
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 8.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The study will assess the efficacy of EP2006 compared to Filgrastim with respect to the mean duration of severe neutropenia during treatment with myelosuppressive chemotherapy in breast cancer patients.

Condition or Disease	Intervention/Treatment	Phase
Chemotherapy Associated Neutropenia; Breast Cancer	Drug: EP2006; Drug: Filgrastim	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 218 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: A Randomized, Double-blind, Parallel-group, Multi-center Phase III Study Comparing the Efficacy and Safety of EP2006 and Neupogen® in Breast Cancer Patients Treated With Myelosuppressive Chemotherapy
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EP2006 Eligible patients will be teated with EP2006	Drug: EP2006; Eligible patients will be teated with EP2006; Other Names: Filgrastim
Active Comparator: Filgrastim Eligible patients will be teated with Filgrastim	Drug: Filgrastim; Eligible patients will be teated with Filgrastim

Outcome Measures

Primary Outcome Measures

1. Mean Duration of Grade 4 Neutropenia During Cycle 1 of Chemotherapy [21 days (Cycle 1 of chemotherapy treatment)]

   Mean duration of severe neutropenia, defined as the mean number of consecutive days with Grade 4 neutropenia (ANC less than 0.5*10^9 cells/L)

Secondary Outcome Measures

1. Incidence of Febrile Neutropenia [21 weeks/ 6 cycles]

   Incidence of febrile neutropenia by duraton within each cycle and across all cycles. Febrile neutropenia is defined as oral temperature greater than or equal 38.3°C while having an Absolute Neutrophil Count < 0.5*10^9 cells/L (both measured on the same day)

2. Number of Days of Fever [21 weeks/ 6 cycles]

   Number of days of fever by cycle. Fever is defined as oral temperature greater than or equal to 38.3°C.

3. Depth of Absolute Neutrophil Count Nadir [Cycle 1/ 21 days]

   Depth of Absolute Neutrophil Count Nadir, defined as the patient's lowest Absolute Neutrophil Count in cycle 1

4. Time to Absolute Neutrophil Count Recovery [Cycle 1/ 21 days]

   Time to Absolute Neutrophil Count recovery, defined as the time in days from Absolute Neutrophil Count nadir until the patient's Absolute Neutrophil Count increases to more or equal to 2*10^9 cells/L after the nadir in cycle 1

5. Frequency of Infections [21 Weeks/ 6 cycles]

   Frequency of infections by cycle and across all cycles

6. Incidence of Hospitalizations Due to Febrile Neutropenia [21 Weeks/ 6 cycles]

   Incidence of hospitalizations due to Febrile Neutropenia

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patients with histologically proven breast cancer, eligible for neoadjuvant or adjuvant myelosuppressive chemotherapy

2. Women ≥ 18 years of age

3. Estimated life expectancy of more than six months

Exclusion Criteria:

1. Previous or concurrent malignancy except non-invasive non-melanoma skin cancer, in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least ten years prior to study entry

2. Any serious illness or medical condition that may interfere with safety, compliance, response to the products under investigation and their evaluation, e.g.:

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Insitut Onkologie a Rehabilitaca na Plesi	Ves pod Plesi 110		Czech Republic	26204
2	Semmelweis Egyetem, III. Belgyogyaszati Klinika	Budapest		Hungary	1125
3	Fovarosi Onkormanyzat Uzsoki utcai Korhaz, Onkoradiologia	Budapest		Hungary	1145
4	DE OEC, Onkologiai Tanszek	Debrecen		Hungary	4032
5	Josa Andras Oktato Korhaz Nonprofit Kft	Nyiregyhaza		Hungary	4400
6	Fejer Megyei Szent Gyorgy Korhaz, Onkologiai Osztaly	Szekesfehervar		Hungary	8000
7	Vas Megyei Markusovszky Korhaz, Onkoradiologiai Osztaly	Szombathely		Hungary	9700
8	Daugavpils Regional Hospital	Daugavpils		Latvia	5400
9	Institution of the Russian Academy of Medical Sciences Medical Radiology Research Center RAMS	Moscow	Krasnogorsk district	Russian Federation	143423
10	State Healthcare Institution (SHI) "Leningrad Regional Oncological Dispensary" at the Surgery Department 2	Kuzmolovsky	Leningrad region	Russian Federation	188663
11	State Medical-Prophylactic Institution SMPI Reginal Clinical Oncological Dispensary	Chelyabinsk		Russian Federation	454087
12	State Healthcare Institution (SHI) "Clinical Oncological Dispensary №1" of Healthcare Department of Krasnodar Territory	Krasnodar		Russian Federation	350040
13	Institution of the Russian Academy of Medical Sciences Russian Oncology Research Center n.a. N.N.Blochin of RAMS", Surgery Department of the Female Reproductive System Tumors	Moscow		Russian Federation	115478
14	Affiliate No1 of State Healthcare Institution (SHI) "Nizhny Novgorod Regional Oncological Dispensary"	Nizhny Novgorod		Russian Federation	603081
15	Institution of the Russian Academy of Medical Sciences Medical Radiology Research Center RAMS	Obninsk		Russian Federation	249036
16	State Healthcare Institution SHI Pyatigorsk Oncological Dispensary	Pyatigorsk		Russian Federation	357502
17	Non-State Healthcare Institution NSHI	Saint-Petersburg		Russian Federation	195271
18	Saint-Petersburg State Healthcare Institution (SPb SHI) "City Clinical Oncological Dispensary"	Saint-Petersburg		Russian Federation	197022
19	State Healthcare Institution (SHI)"Voronezh Regional Clinical Oncological Dispensary"	Voronezh		Russian Federation	394000
20	Fakultna nemocnica Nitra, Oddelenie radioterapie a klinickej onkologie	Nitra		Slovakia	95001
21	Communal Institution "Krivorizhskiy oncology dispensary" of Dnipropetrovsk regional Council, Chemotherapy Department	Kriviy Rig	Dnipropetrovsk region	Ukraine	50048
22	Communal Institution "Dnipropetrovsk Сity multiple-discipline Clinical Hospital 4" of Dnipropetrovsk Regional Council	Dnipropetrovsk		Ukraine	49102
23	Medical center of Limited Liability Company "Inter"	Lugansk		Ukraine	91000
24	Lviv state oncological regional treatment-and-diagnostics center, Chemotherapy Department	Lviv		Ukraine	79031
25	Communal Institution "Odesa regional clinical hospital", Mammology Center	Odesa		Ukraine	65025
26	Vinnytsya Regional Clinical Oncological Center, Chemotherapy Department	Vinnitsya		Ukraine	21029

Sponsors and Collaborators

• Sandoz

Investigators

• Study Chair: Sandoz, Sandoz

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT01519700
• Other Study ID Numbers: EP06-302; 2010-024481-22
• First Posted: Jan 27, 2012
• Last Update Posted: May 6, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Sandoz: Filgrastim; G-CSF, neutropenia; supportive care; breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Neutropenia; Lenograstim

Study Results

Participant Flow

Recruitment Details	The study population consisted of women of 18 years or older with histologically proven breast cancer who were eligible for neoadjuvant or adjuvant treatment with TAC chemotherapy. The study was aimed to randomize a total of 192 patients in approximately 65 centers worldwide.
Pre-assignment Detail	The study started with a screening period of up to 21 days. During the screening period, the eligibility of the patients to participate in the study was assessed based on safety evaluations. After completion of the screening period, the patients were randomized to either EP2006 or US-licensed Neupogen® in four groups (see below).

Arm/Group Title	EP2006	EP2006 + Neupogen	Neupogen + EP2006	Neupogen
Arm/Group Description	Patients remained on EP2006 (their initial treatment) throughout the study daily dose of 5 mcg/kg body weight, subcutaneously	Patients received alternating treatment with EP2006 or Neupogen starting with the second cycle, daily dose of 5 mcg/kg body weight, subcutaneously	Patients received alternating treatment with Neupogen or EP2006 starting with the 2nd cycle, daily dose of 5 mcg/kg body weight, subcutaneously	Patients remained on Neupogen (their initial treatment) throughout the study, daily dose of 5 mcg/kg body weight, subcutaneously
Period Title: Overall Study
STARTED	54	55	55	54
Treated Cycle 1 EP2006	53	54	0	0
Treated Cycle 1 Neupogen	0	0	55	52
Treated Cycle 2 EP2006	52	0	55	0
Treated Cycle 2 Neupogen	0	52	0	51
Treated Cycle 3 EP2006	51	51	0	0
Treated Cycle 3 Neupogen	0	0	54	51
Treated Cycle 4 EP2006	51	0	50	0
Treated Cycle 4 Neupogen	0	51	0	50
Treated Cycle 5 EP2006	46	49	0	0
Treated Cycle 5 Neupogen	0	0	48	50
Treated Cycle 6 EP2006	45	0	48	0
Treated Cycle 6 Neupogen	0	49	0	49
COMPLETED	45	49	48	47
NOT COMPLETED	9	6	7	7

Baseline Characteristics

Arm/Group Title	EP2006	EP2006 + Neupogen	Neupogen + EP2006	Neupogen	Total
Arm/Group Description	Patients remained on EP2006 (their initial treatment) throughout the study	Patients received alternating treatment with EP2006 or Neupogen starting with the second cycle	Patients received alternating treatment with Neupogen or EP2006 starting with the 2nd cycle	Patients remained on Neupogen (their initial treatment) throughout the study	Total of all reporting groups
Overall Participants	53	54	55	52	214
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.5 (11.16)	47.5 (11.64)	49.7 (11.05)	46.9 (10.91)	48.9 (11.26)
Sex: Female, Male (Count of Participants)
Female	53 100%	54 100%	55 100%	52 100%	214 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Mean Duration of Grade 4 Neutropenia During Cycle 1 of Chemotherapy
Description	Mean duration of severe neutropenia, defined as the mean number of consecutive days with Grade 4 neutropenia (ANC less than 0.5*10^9 cells/L)
Time Frame	21 days (Cycle 1 of chemotherapy treatment)

Outcome Measure Data

Analysis Population Description

PP population

Arm/Group Title	EP2006 + EP2006 & Neupogen	Neupogen + Neupogen & EP2006
Arm/Group Description	All subjects randomized to receive either EP2006 in Cycle 1	All subjects randomized to receive Neupogen in Cycle 1
Measure Participants	101	103
Mean (Standard Deviation) [Days]	1.17 (1.11)	1.2 (1.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EP2006 + EP2006 & Neupogen
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority limit: -1 day Power: 90% Confidence level: 97.5% Randomization ratio: 1:1 (EP2006:Neupogen)
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.04
	Confidence Interval	(1-Sided) 97.5%; -0.26 to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The one-sided 97.5% Confidence Interval: [-0.26, ∞).

2. Secondary Outcome

Title	Incidence of Febrile Neutropenia
Description	Incidence of febrile neutropenia by duraton within each cycle and across all cycles. Febrile neutropenia is defined as oral temperature greater than or equal 38.3°C while having an Absolute Neutrophil Count < 0.5*10^9 cells/L (both measured on the same day)
Time Frame	21 weeks/ 6 cycles

Outcome Measure Data

Analysis Population Description

SAF-I (alternating safety) set: patients who received at least one dose of study medication after Cycle 1.

Arm/Group Title	EP2006	EP2006 + Neupogen	Neupogen + EP2006	Neupogen	Total
Arm/Group Description	Patients remained on EP2006 (their initial treatment) throughout the study	Patients received alternating treatment with EP2006 or Neupogen starting with the second cycle	Patients received alternating treatment with Neupogen or EP2006 starting with the 2nd cycle	Patients remained on Neupogen (their initial treatment) throughout the study	All patients
Measure Participants	52	52	55	51	210
Cycle 1 - 0 Days duration	50 94.3%	49 90.7%	54 98.2%	51 98.1%	204 95.3%
Cycle 1 - 1 Day duration	2 3.8%	3 5.6%	0 0%	0 0%	5 2.3%
Cycle 1 - 2 Days duration	0 0%	0 0%	1 1.8%	0 0%	1 0.5%
Cycle 2 - 0 Days duration	52 98.1%	51 94.4%	55 100%	51 98.1%	209 97.7%
Cycle 2 - 1 Day duration	0 0%	1 1.9%	0 0%	0 0%	1 0.5%
Cycle 3 - 0 Days duration	51 96.2%	51 94.4%	54 98.2%	51 98.1%	207 96.7%
Cycle 4 - 0 Days duration	51 96.2%	51 94.4%	50 90.9%	50 96.2%	202 94.4%
Cycle 5 - 0 Days duration	45 84.9%	48 88.9%	48 87.3%	50 96.2%	191 89.3%
Cycle 5 - 1 Day duration	0 0%	1 1.9%	0 0%	0 0%	1 0.5%
Cycle 6 - 0 Days duration	43 81.1%	48 88.9%	48 87.3%	49 94.2%	188 87.9%
Cycle 6 - 1 Day duration	1 1.9%	1 1.9%	0 0%	0 0%	2 0.9%
All Cycles - 0 Days duration	49 92.5%	46 85.2%	54 98.2%	51 98.1%	200 93.5%
All Cycles - 1 Day duration	3 5.7%	6 11.1%	0 0%	0 0%	9 4.2%
All Cycles - 2 Days duration	0 0%	0 0%	1 1.8%	0 0%	1 0.5%

3. Secondary Outcome

Title	Number of Days of Fever
Description	Number of days of fever by cycle. Fever is defined as oral temperature greater than or equal to 38.3°C.
Time Frame	21 weeks/ 6 cycles

Outcome Measure Data

Analysis Population Description

PP-I (alternating Per-Protocol) set: randomized patients who completed all six chemotherapy cycles without major protocol violations.

Arm/Group Title	EP2006	EP2006 + Neupogen	Neupogen + EP2006	Neupogen	Total
Arm/Group Description	Patients remained on EP2006 (their initial treatment) throughout the study	Patients received alternating treatment with EP2006 or Neupogen starting with the second cycle	Patients received alternating treatment with Neupogen or EP2006 starting with the 2nd cycle	Patients remained on Neupogen (their initial treatment) throughout the study	All patients
Measure Participants	40	45	44	46	175
Cycle 1 - No	39 73.6%	41 75.9%	42 76.4%	46 88.5%	168 78.5%
Cycle 1 - Yes	1 1.9%	4 7.4%	2 3.6%	0 0%	7 3.3%
Cycle 2 - No	36 67.9%	43 79.6%	44 80%	46 88.5%	169 79%
Cycle 2 - Yes	4 7.5%	2 3.7%	0 0%	0 0%	6 2.8%
Cycle 3 - No	40 75.5%	44 81.5%	44 80%	45 86.5%	173 80.8%
Cycle 3 - Yes	0 0%	1 1.9%	0 0%	1 1.9%	2 0.9%
Cycle 4 - No	40 75.5%	44 81.5%	43 78.2%	46 88.5%	173 80.8%
Cycle 4 - Yes	0 0%	1 1.9%	1 1.8%	0 0%	2 0.9%
Cycle 5 - No	40 75.5%	44 81.5%	43 78.2%	45 86.5%	172 80.4%
Cycle 5 - Yes	0 0%	1 1.9%	1 1.8%	1 1.9%	3 1.4%
Cycle 6 - No	39 73.6%	44 81.5%	44 80%	46 88.5%	173 80.8%
Cycle 6 - Yes	1 1.9%	1 1.9%	0 0%	0 0%	2 0.9%

4. Secondary Outcome

Title	Depth of Absolute Neutrophil Count Nadir
Description	Depth of Absolute Neutrophil Count Nadir, defined as the patient's lowest Absolute Neutrophil Count in cycle 1
Time Frame	Cycle 1/ 21 days

Outcome Measure Data

Analysis Population Description

FAS (full analysis) set: all patients who received at least one dose of study medication, analyzed according to randomization allocation

Arm/Group Title	EP2006 + EP2006 & Neupogen	Neupogen + Neupogen & EP2006	Total
Arm/Group Description	All subjects randomized to receive either EP2006 in Cycle 1	All subjects randomized to receive Neupogen in Cycle 1	All patients in Cycle 1
Measure Participants	107	107	214
Mean (Standard Deviation) [10^9 cells/L]	0.808 (1.3694)	0.744 (1.2906)	0.776 (1.3278)

5. Secondary Outcome

Title	Time to Absolute Neutrophil Count Recovery
Description	Time to Absolute Neutrophil Count recovery, defined as the time in days from Absolute Neutrophil Count nadir until the patient's Absolute Neutrophil Count increases to more or equal to 2*10^9 cells/L after the nadir in cycle 1
Time Frame	Cycle 1/ 21 days

Outcome Measure Data

Analysis Population Description

FAS (full analysis) set: all patients who received at least one dose of study medication, analyzed according to randomization allocation. In the EP2006 + EP2006 & Neupogen group, one patient's time to Absolute Neutrophil Count recovery could not be measured as the nadir was the last measured timepoint.

Arm/Group Title	EP2006 + EP2006 & Neupogen	Neupogen + Neupogen & EP2006	Total
Arm/Group Description	All subjects randomized to receive either EP2006 in Cycle 1	All subjects randomized to receive Neupogen in Cycle 1	All patients in Cycle 1
Measure Participants	106	107	213
Median (Full Range) [Days]	2.0	2.0	2.0

6. Secondary Outcome

Title	Frequency of Infections
Description	Frequency of infections by cycle and across all cycles
Time Frame	21 Weeks/ 6 cycles

Outcome Measure Data

Analysis Population Description

SAF-I (alternating safety) set: patients who received at least one dose of study medication after Cycle 1. Comparison made for alternating versus non-alternating treatment groups.

Arm/Group Title	EP2006 + Neupogen	EP2006 & Neupogen + Neupogen & EP2006	Total
Arm/Group Description	All subjects randomized to receive either EP2006 or Neupogen.	All subjects randomized to receive EP2006 & Neupogen + Neupogen & EP2006.	All patients in Cycle 1
Measure Participants	103	107	210
Cycle 1 - No	102 192.5%	104 192.6%	206 374.5%
Cycle 1 - Yes	1 1.9%	3 5.6%	4 7.3%
Cycle 2 - No	100 188.7%	102 188.9%	202 367.3%
Cycle 2 - Yes	3 5.7%	5 9.3%	8 14.5%
Cycle 3 - No	102 192.5%	107 198.1%	209 380%
Cycle 3 - Yes	1 1.9%	0 0%	1 1.8%
Cycle 4 - No	101 190.6%	104 192.6%	205 372.7%
Cycle 4 - Yes	2 3.8%	3 5.6%	5 9.1%
Cycle 5 - No	101 190.6%	106 196.3%	207 376.4%
Cycle 5 - Yes	2 3.8%	1 1.9%	3 5.5%
Cycle 6 - No	102 192.5%	106 196.3%	208 378.2%
Cycle 6 - Yes	1 1.9%	1 1.9%	2 3.6%
All Cycles - No	96 181.1%	97 179.6%	193 350.9%
All Cycles - Yes	7 13.2%	10 18.5%	17 30.9%

7. Secondary Outcome

Title	Incidence of Hospitalizations Due to Febrile Neutropenia
Description	Incidence of hospitalizations due to Febrile Neutropenia
Time Frame	21 Weeks/ 6 cycles

Outcome Measure Data

Analysis Population Description

SAF-I (alternating safety) set: patients who received at least one dose of study medication after Cycle 1.

Arm/Group Title	EP2006	EP2006 + Neupogen	Neupogen + EP2006	Neupogen	Total
Arm/Group Description	Patients remained on EP2006 (their initial treatment) throughout the study	Patients received alternating treatment with EP2006 or Neupogen starting with the second cycle	Patients received alternating treatment with Neupogen or EP2006 starting with the 2nd cycle	Patients remained on Neupogen (their initial treatment) throughout the study	All patients
Measure Participants	52	52	55	51	210
No	50 94.3%	50 92.6%	55 100%	51 98.1%	206 96.3%
Yes	2 3.8%	1 1.9%	0 0%	1 1.9%	4 1.9%

Adverse Events

Arm/Group Title	EP2006		EP2006 + Neupogen		Neupogen + EP2006		Neupogen
Arm/Group Description	Patients remained on EP2006 (their initial treatment) throughout the study		Patients received alternating treatment with EP2006 or Neupogen starting with the second cycle		Patients received alternating treatment with Neupogen or EP2006 starting with the 2nd cycle		Patients remained on Neupogen (their initial treatment) throughout the study
All Cause Mortality
	EP2006		EP2006 + Neupogen		Neupogen + EP2006		Neupogen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	EP2006		EP2006 + Neupogen		Neupogen + EP2006		Neupogen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/53 (11.3%)		4/54 (7.4%)		1/55 (1.8%)		3/52 (5.8%)
Blood and lymphatic system disorders
Febrile Neutropenia	3/53 (5.7%)	3	4/54 (7.4%)	4	1/55 (1.8%)	1	1/52 (1.9%)	1
Anaemia	0/53 (0%)	0	0/54 (0%)	0	0/55 (0%)	0	1/52 (1.9%)	1
Leukopenia	1/53 (1.9%)	1	0/54 (0%)	0	0/55 (0%)	0	0/52 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/53 (0%)	0	0/54 (0%)	0	0/55 (0%)	0	1/52 (1.9%)	1
Vascular disorders
Embolism	1/53 (1.9%)	1	0/54 (0%)	0	0/55 (0%)	0	0/52 (0%)	0
Hypertensive crisis	1/53 (1.9%)	1	0/54 (0%)	0	0/55 (0%)	0	0/52 (0%)	0
Other (Not Including Serious) Adverse Events
	EP2006		EP2006 + Neupogen		Neupogen + EP2006		Neupogen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/53 (94.3%)		51/54 (94.4%)		52/55 (94.5%)		50/52 (96.2%)
Blood and lymphatic system disorders
Neutropenia	5/53 (9.4%)	21	7/54 (13%)	18	6/55 (10.9%)	20	6/52 (11.5%)	22
Anaemia	6/53 (11.3%)	10	5/54 (9.3%)	9	4/55 (7.3%)	6	11/52 (21.2%)	24
Leucopenia	4/53 (7.5%)	21	4/54 (7.4%)	12	2/55 (3.6%)	3	3/52 (5.8%)	9
Febrile neutropenia	3/53 (5.7%)	3	5/54 (9.3%)	5	1/55 (1.8%)	1	1/52 (1.9%)	1
Gastrointestinal disorders
Nausea	29/53 (54.7%)	103	33/54 (61.1%)	95	32/55 (58.2%)	116	37/52 (71.2%)	149
Diarrhoea	5/53 (9.4%)	8	11/54 (20.4%)	14	13/55 (23.6%)	21	8/52 (15.4%)	11
Vomiting	9/53 (17%)	27	10/54 (18.5%)	22	10/55 (18.2%)	21	9/52 (17.3%)	19
Abdominal pain upper	2/53 (3.8%)	3	0/54 (0%)	0	5/55 (9.1%)	10	2/52 (3.8%)	2
Abdominal pain	3/53 (5.7%)	8	2/54 (3.7%)	2	4/55 (7.3%)	7	3/52 (5.8%)	6
Stomatitis	3/53 (5.7%)	3	3/54 (5.6%)	3	0/55 (0%)	0	2/52 (3.8%)	4
General disorders
Asthenia	20/53 (37.7%)	66	28/54 (51.9%)	98	32/55 (58.2%)	111	28/52 (53.8%)	101
Fatigue	17/53 (32.1%)	52	9/54 (16.7%)	17	11/55 (20%)	38	13/52 (25%)	38
Hypothermia	0/53 (0%)	0	3/54 (5.6%)	6	1/55 (1.8%)	14	1/52 (1.9%)	1
Pyrexia	6/53 (11.3%)	9	3/54 (5.6%)	8	1/55 (1.8%)	1	1/52 (1.9%)	2
Metabolism and nutrition disorders
Decreased Appetite	8/53 (15.1%)	21	4/54 (7.4%)	8	3/55 (5.5%)	6	13/52 (25%)	32
Musculoskeletal and connective tissue disorders
Bone pain	13/53 (24.5%)	33	20/54 (37%)	46	19/55 (34.5%)	60	19/52 (36.5%)	60
Arthralgia	3/53 (5.7%)	8	4/54 (7.4%)	4	6/55 (10.9%)	8	3/52 (5.8%)	3
Myalgia	2/53 (3.8%)	5	3/54 (5.6%)	4	3/55 (5.5%)	5	3/52 (5.8%)	4
Musculosceletal pain	5/53 (9.4%)	6	1/54 (1.9%)	2	2/55 (3.6%)	3	1/52 (1.9%)	3
Nervous system disorders
Dizziness	3/53 (5.7%)	8	0/54 (0%)	0	3/55 (5.5%)	4	1/52 (1.9%)	1
Headache	3/53 (5.7%)	6	3/54 (5.6%)	3	2/55 (3.6%)	2	1/52 (1.9%)	1
Periferal sensory neur.	3/53 (5.7%)	3	0/54 (0%)	0	2/55 (3.6%)	2	1/52 (1.9%)	1
Skin and subcutaneous tissue disorders
Alopecia	41/53 (77.4%)	43	44/54 (81.5%)	45	43/55 (78.2%)	46	43/52 (82.7%)	44
Erythema	5/53 (9.4%)	15	2/54 (3.7%)	3	6/55 (10.9%)	19	6/52 (11.5%)	23
Vascular disorders
Flushing	1/53 (1.9%)	3	3/54 (5.6%)	10	0/55 (0%)	0	2/52 (3.8%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI shall provide Sponsor with any presentation at least 15 working days prior to disclosure and any other publication at least 45 working days prior to disclosure. Sponsor may require amendments on reasonable grounds: (a) accuracy of publication; (b) confidentiality of proprietary information; (c) intellectual property protection; (d) to enable further information to be provided. Sponsor may require publications or presentations to be delayed up to four (4) months to enable patent application.