Pemetrexed Plus Gemcitabine in Metastatic Breast Cancer Patients After Receiving Taxane Therapy

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00063570
• Collaborator: (none)
• Enrollment: 73
• Locations: 7
• Arms: 2
• Duration (Months): 54
• Patients Per Site: 10.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the study is to determine if the two drugs can help patients feel better while causing the tumor to become smaller or disappear; evaluate the safety of giving both pemetrexed and gemcitabine in patients with advanced breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Breast Neoplasms	Drug: Pemetrexed; Drug: Gemcitabine; Drug: Gemcitabine; Drug: Pemetrexed	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Alimta (Pemetrexed) and Gemzar (Gemcitabine) in Metastatic Breast Cancer Patients Who Have Received Prior Taxane Therapy
• Study Start Date: Jul 1, 2003
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: Pemetrexed; 500 mg/m2, intravenous (IV), every 14 days, until disease progression; Other Names: LY231514, Alimta ; Drug: Gemcitabine; 1500 mg/m2, intravenous (IV), every 14 days, until disease progression; Other Names: LY188011, Gemzar
Experimental: B	Drug: Gemcitabine; 1000 mg/m2, intravenous (IV), on Days 1 and 8 of 21-day cycle, until disease progression; Other Names: LY188011 Gemzar ; Drug: Pemetrexed; 500 mg/m2, intravenous (IV), every 21 days, until disease progression; Other Names: LY231514 Alimta

Outcome Measures

Primary Outcome Measures

1. Overall Tumor Response [Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated]

   Best overall (confirmed) response recorded from start of treatment until disease progression/recurrence, start of other anti-tumor therapy/intervention, or end of trial, whichever comes first. Response must be confirmed at least 6 weeks from previous scans. Best overall response assignment depends on both measurement and confirmation criteria.

Secondary Outcome Measures

1. Duration of (Confirmed) Complete Response or Partial Response [Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated]

   Duration of response is calculated as (Date of First Disease Progression or Death as a Result of any Cause whichever Comes First - Date of First Objective Status Assessment of Confirmed CR or PR + 1)/(365.25/12).

2. Time to Progressive Disease [Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated]

   Time to progressive disease is calculated as (Date of First Disease Progression or Death Due to Disease under Study whichever Comes First - First Dose Date + 1)/(365.25/12).

3. Time to Treatment Failure [Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated]

   Time to treatment failure is calculated as (Date of First Disease Progression, Death as a Result of any Cause, or Early Discontinuation of Treatment Due to Adverse Event or Physician Perception of Lack of Efficacy or Patient and Physician Perception of Lack of Efficacy, whichever Comes First - First Dose Date + 1)/ (365.25/12)

4. Overall Survival [Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated]

   Overall survival time is calculated as (Date of Death as a Result of any Cause - First Dose Date + 1)/ (365.25/12).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Must have received prior chemotherapy with Taxol (paclitaxel) or Taxotere (docetaxel).

• Less than 3 different chemotherapy treatments for metastatic disease.

• Prior treatment with hormonal and/or radiation therapy.

• Must have disease that can be measured.

• Must be able to take care of self needs for example personal hygiene

Exclusion Criteria:

• Must not be pregnant or breast-feeding.

• Cancer that has spread to the brain.

• Treatment with Gemcitabine or Pemetrexed

• Unable to take folic acid or Vitamin B12

• Treatment for another cancer within the last 5 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Aurora	Colorado	United States
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Plantation	Florida	United States
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Morrisville	North Carolina	United States
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Philadelphia	Pennsylvania	United States
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Dallas	Texas	United States
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Seattle	Washington	United States
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	San Juan		Puerto Rico

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 317-615-4559 Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00063570
• Other Study ID Numbers: 5141; H3E-US-JMEO
• First Posted: Jul 1, 2003
• Last Update Posted: May 29, 2009
• Last Verified: May 1, 2009

• Keywords provided by , ,: Cancer of Breast; Cancer of the Breast
• Additional relevant MeSH terms: Breast Neoplasms; Gemcitabine; Pemetrexed

Study Results

Participant Flow

Pre-assignment Detail	At completion of the first stage of the trial, toxicities associated with the Day 8 dosing of gemcitabine were observed, and the protocol was amended to a bi-weekly schedule. Patients were analyzed separately according to the study drug schedule received.

Arm/Group Title	Bi-Weekly Schedule	21-Day Schedule
Arm/Group Description	Pemetrexed: 500 mg/m2, intravenous (IV), every 14 days, until disease progression. Gemcitabine: 1500 mg/m2, intravenous (IV), every 14 days, until disease progression.	Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days, until disease progression. Gemcitabine: 1000 mg/m2, intravenous (IV) on Days 1 and 8 of a 21-day cycle, until disease progression.
Period Title: Overall Study
STARTED	52	21
COMPLETED	52	21
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Bi-Weekly Schedule	21-Day Schedule	Total
Arm/Group Description	Pemetrexed: 500 mg/m2, intravenous (IV), every 14 days, until disease progression. Gemcitabine: 1500 mg/m2, intravenous (IV), every 14 days, until disease progression.	Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days, until disease progression. Gemcitabine: 1000 mg/m2, intravenous (IV) on Days 1 and 8 of a 21-day cycle, until disease progression.	Total of all reporting groups
Overall Participants	52	21	73
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53.5	50.7	51.9
Sex: Female, Male (Count of Participants)
Female	52 100%	21 100%	73 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	52 100%	21 100%	73 100%
Current Pathological Diagnosis (paticipants) [Number]
Ductal breast carcinoma	36	12	48
Lobular breast carcinoma	2	0	2
Adenocystic breast carcinoma	0	1	1
Breast carcinoma	4	4	8
Other	7	3	10
Unknown	1	1	2
No current pathological diagnosis	2	0	2
Karnofsky Performance Status (KPS) (participants) [Number]
<=60 - Needs increasing assistance up to Death (0)	0 0%	0 0%	0 0%
70 - Unable to carry on normal activity	4 7.7%	1 4.8%	5 6.8%
80 - Activity with effort; some signs of disease	11 21.2%	5 23.8%	16 21.9%
90 - Normal activity; minor signs of disease	19 36.5%	9 42.9%	28 38.4%
100 - Normal no complaints; no evidence of disease	17 32.7%	6 28.6%	23 31.5%
unknown	1 1.9%	0 0%	1 1.4%
Menopausal Status at Cycle 0 (participants) [Number]
Pre-Menopausal	7 13.5%	3 14.3%	10 13.7%
Menopausal	4 7.7%	3 14.3%	7 9.6%
Post-Menopausal	41 78.8%	15 71.4%	56 76.7%
Patients with Current Pathological Diagnosis (participants) [Number]
Yes	50 96.2%	21 100%	71 97.3%
No	2 3.8%	0 0%	2 2.7%
Race/Ethnicity (participants) [Number]
Caucasian	44 84.6%	20 95.2%	64 87.7%
African	4 7.7%	1 4.8%	5 6.8%
East/Southeast Asian	3 5.8%	0 0%	3 4.1%
Hispanic	1 1.9%	0 0%	1 1.4%
Time (in months) from Current Pathological Diagnosis to Enrollment (Months) [Median (Full Range) ]
Median (Full Range) [Months]	13.08	14.31	14.29

Outcome Measures

1. Primary Outcome

Title	Overall Tumor Response
Description	Best overall (confirmed) response recorded from start of treatment until disease progression/recurrence, start of other anti-tumor therapy/intervention, or end of trial, whichever comes first. Response must be confirmed at least 6 weeks from previous scans. Best overall response assignment depends on both measurement and confirmation criteria.
Time Frame	Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated

Outcome Measure Data

Analysis Population Description

Patients who received at least one dose of study drug (pemetrexed or gemcitabine) were included in the analyses.

Arm/Group Title	Bi-Weekly Schedule	21-Day Schedule
Arm/Group Description	Pemetrexed: 500 mg/m2, intravenous (IV), every 14 days, until disease progression. Gemcitabine: 1500 mg/m2, intravenous (IV), every 14 days, until disease progression.	Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days, until disease progression. Gemcitabine: 1000 mg/m2, intravenous (IV) on Days 1 and 8 of a 21-day cycle, until disease progression.
Measure Participants	52	21
Complete Response	2 3.8%	0 0%
Partial Response	8 15.4%	5 23.8%
Stable Disease	26 50%	10 47.6%
Progressive Disease	14 26.9%	6 28.6%
Unknown	2 3.8%	0 0%

2. Secondary Outcome

Title	Duration of (Confirmed) Complete Response or Partial Response
Description	Duration of response is calculated as (Date of First Disease Progression or Death as a Result of any Cause whichever Comes First - Date of First Objective Status Assessment of Confirmed CR or PR + 1)/(365.25/12).
Time Frame	Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated

Outcome Measure Data

Analysis Population Description

Number of patients with a confirmed complete or partial response.

Arm/Group Title	Bi-Weekly Schedule	21-Day Schedule
Arm/Group Description	Pemetrexed: 500 mg/m2, intravenous (IV), every 14 days, until disease progression. Gemcitabine: 1500 mg/m2, intravenous (IV), every 14 days, until disease progression.	Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days, until disease progression. Gemcitabine: 1000 mg/m2, intravenous (IV) on Days 1 and 8 of a 21-day cycle, until disease progression.
Measure Participants	10	5
Median (Full Range) [months]	5.85	4.17

3. Secondary Outcome

Title	Time to Progressive Disease
Description	Time to progressive disease is calculated as (Date of First Disease Progression or Death Due to Disease under Study whichever Comes First - First Dose Date + 1)/(365.25/12).
Time Frame	Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated

Outcome Measure Data

Analysis Population Description

Intention to Treat analysis

Arm/Group Title	Bi-Weekly Schedule	21-Day Schedule
Arm/Group Description	Pemetrexed: 500 mg/m2, intravenous (IV), every 14 days, until disease progression. Gemcitabine: 1500 mg/m2, intravenous (IV), every 14 days, until disease progression.	Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days, until disease progression. Gemcitabine: 1000 mg/m2, intravenous (IV) on Days 1 and 8 of a 21-day cycle, until disease progression.
Measure Participants	52	21
Median (Full Range) [months]	3.19	4.01

4. Secondary Outcome

Title	Time to Treatment Failure
Description	Time to treatment failure is calculated as (Date of First Disease Progression, Death as a Result of any Cause, or Early Discontinuation of Treatment Due to Adverse Event or Physician Perception of Lack of Efficacy or Patient and Physician Perception of Lack of Efficacy, whichever Comes First - First Dose Date + 1)/ (365.25/12)
Time Frame	Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated

Outcome Measure Data

Analysis Population Description

Intention to Treat analysis

Arm/Group Title	Bi-Weekly Schedule	21-Day Schedule
Arm/Group Description	Pemetrexed: 500 mg/m2, intravenous (IV), every 14 days, until disease progression. Gemcitabine: 1500 mg/m2, intravenous (IV), every 14 days, until disease progression.	Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days, until disease progression. Gemcitabine: 1000 mg/m2, intravenous (IV) on Days 1 and 8 of a 21-day cycle, until disease progression.
Measure Participants	52	21
Median (Full Range) [months]	2.79	2.56

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival time is calculated as (Date of Death as a Result of any Cause - First Dose Date + 1)/ (365.25/12).
Time Frame	Every 6 weeks from start of treatment until documented disease progression or for 6 months from last dose of study drug, whichever occurs first. After 6 months, clinical assessment every 12 weeks and radiologic test performed as clinically indicated

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bi-Weekly Schedule	21-Day Schedule
Arm/Group Description	Pemetrexed: 500 mg/m2, intravenous (IV), every 14 days, until disease progression. Gemcitabine: 1500 mg/m2, intravenous (IV), every 14 days, until disease progression.	Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days, until disease progression. Gemcitabine: 1000 mg/m2, intravenous (IV) on Days 1 and 8 of a 21-day cycle, until disease progression.
Measure Participants	52	21
Median (Full Range) [months]	13.44	16.20

Adverse Events

Arm/Group Title	Bi-Weekly Schedule		21-Day Schedule
Arm/Group Description	Pemetrexed: 500 mg/m2, intravenous (IV), every 14 days, until disease progression. Gemcitabine: 1500 mg/m2, intravenous (IV), every 14 days, until disease progression.		Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days, until disease progression. Gemcitabine: 1000 mg/m2, intravenous (IV) on Days 1 and 8 of a 21-day cycle, until disease progression.
All Cause Mortality
	Bi-Weekly Schedule		21-Day Schedule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bi-Weekly Schedule		21-Day Schedule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/ (NaN)		7/ (NaN)
Blood and lymphatic system disorders
Anaemia	2/52 (3.8%)	2	0/21 (0%)	0
Febrile neutropenia	4/52 (7.7%)	5	1/21 (4.8%)	1
Pancytopenia	1/52 (1.9%)	1	0/21 (0%)	0
Thrombocytopenia	0/52 (0%)	0	1/21 (4.8%)	1
Gastrointestinal disorders
Abdominal pain	1/52 (1.9%)	1	0/21 (0%)	0
Constipation	1/52 (1.9%)	1	0/21 (0%)	0
General disorders
Pyrexia	2/52 (3.8%)	3	1/21 (4.8%)	1
Hepatobiliary disorders
Hepatic failure	1/52 (1.9%)	2	0/21 (0%)	0
Hyperbilirubinaemia	1/52 (1.9%)	1	0/21 (0%)	0
Infections and infestations
Device related infection	1/52 (1.9%)	1	0/21 (0%)	0
Pneumonia	2/52 (3.8%)	2	0/21 (0%)	0
Sepsis	1/52 (1.9%)	1	0/21 (0%)	0
Injury, poisoning and procedural complications
Femur fracture	0/52 (0%)	0	1/21 (4.8%)	1
Fracture	1/52 (1.9%)	1	0/21 (0%)	0
Spinal compression fracture	1/52 (1.9%)	1	0/21 (0%)	0
Investigations
Drug level increased	1/52 (1.9%)	1	0/21 (0%)	0
Metabolism and nutrition disorders
Dehydration	2/52 (3.8%)	2	0/21 (0%)	0
Hyponatraemia	1/52 (1.9%)	1	0/21 (0%)	0
Hypovolaemia	1/52 (1.9%)	1	0/21 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	1/52 (1.9%)	1	0/21 (0%)	0
Nervous system disorders
Convulsion	1/52 (1.9%)	1	0/21 (0%)	0
Dizziness	0/52 (0%)	0	1/21 (4.8%)	1
Lumbar radiculopathy	1/52 (1.9%)	1	0/21 (0%)	0
Meningitis noninfective	1/52 (1.9%)	1	0/21 (0%)	0
Psychiatric disorders
Mental status changes	1/52 (1.9%)	1	0/21 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/52 (0%)	0	1/21 (4.8%)	1
Interstitial lung disease	1/52 (1.9%)	1	0/21 (0%)	0
Pleural effusion	2/52 (3.8%)	2	0/21 (0%)	0
Pneumonitis	1/52 (1.9%)	1	0/21 (0%)	0
Pulmonary embolism	0/52 (0%)	0	1/21 (4.8%)	1
Pulmonary oedema	0/52 (0%)	0	1/21 (4.8%)	1
Respiratory failure	1/52 (1.9%)	1	0/21 (0%)	0
Skin and subcutaneous tissue disorders
Drug eruption	1/52 (1.9%)	1	0/21 (0%)	0
Erythema	0/52 (0%)	0	1/21 (4.8%)	1
Vascular disorders
Aortic stenosis	0/52 (0%)	0	1/21 (4.8%)	1
Superior vena caval occlusion	0/52 (0%)	0	1/21 (4.8%)	1
Other (Not Including Serious) Adverse Events
	Bi-Weekly Schedule		21-Day Schedule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/ (NaN)		21/ (NaN)
Blood and lymphatic system disorders
Anaemia	23/52 (44.2%)	40	12/21 (57.1%)	22
Febrile neutropenia	2/52 (3.8%)	2	3/21 (14.3%)	3
Leukopenia	13/52 (25%)	18	6/21 (28.6%)	22
Lymphopenia	1/52 (1.9%)	2	2/21 (9.5%)	10
Neutropenia	23/52 (44.2%)	35	16/21 (76.2%)	53
Thrombocythaemia	1/52 (1.9%)	1	2/21 (9.5%)	3
Thrombocytopenia	10/52 (19.2%)	14	8/21 (38.1%)	20
Cardiac disorders
Tachycardia	5/52 (9.6%)	5	1/21 (4.8%)	1
Eye disorders
Diplopia	0/52 (0%)	0	2/21 (9.5%)	4
Eye irritation	4/52 (7.7%)	4	3/21 (14.3%)	4
Eye swelling	3/52 (5.8%)	3	0/21 (0%)	0
Lacrimation increased	8/52 (15.4%)	9	1/21 (4.8%)	1
Vision blurred	3/52 (5.8%)	3	0/21 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	3/52 (5.8%)	3	0/21 (0%)	0
Abdominal distension	5/52 (9.6%)	7	3/21 (14.3%)	3
Abdominal pain	10/52 (19.2%)	13	5/21 (23.8%)	6
Abdominal pain upper	5/52 (9.6%)	6	0/21 (0%)	0
Constipation	26/52 (50%)	40	6/21 (28.6%)	11
Diarrhoea	16/52 (30.8%)	18	12/21 (57.1%)	14
Dry mouth	3/52 (5.8%)	6	0/21 (0%)	0
Dyspepsia	5/52 (9.6%)	5	3/21 (14.3%)	3
Gastrooesophageal reflux disease	6/52 (11.5%)	6	0/21 (0%)	0
Haemorrhoids	3/52 (5.8%)	3	2/21 (9.5%)	2
Nausea	28/52 (53.8%)	46	14/21 (66.7%)	28
Stomatitis	9/52 (17.3%)	12	3/21 (14.3%)	4
Vomiting	10/52 (19.2%)	13	7/21 (33.3%)	16
General disorders
Asthenia	6/52 (11.5%)	9	4/21 (19%)	6
Chest discomfort	3/52 (5.8%)	5	1/21 (4.8%)	2
Chest pain	4/52 (7.7%)	4	4/21 (19%)	5
Chills	7/52 (13.5%)	9	6/21 (28.6%)	7
Face oedema	4/52 (7.7%)	4	0/21 (0%)	0
Fatigue	35/52 (67.3%)	68	15/21 (71.4%)	28
Feeling hot	0/52 (0%)	0	2/21 (9.5%)	2
Mucosal inflammation	6/52 (11.5%)	7	4/21 (19%)	4
Oedema	5/52 (9.6%)	6	1/21 (4.8%)	1
Oedema peripheral	12/52 (23.1%)	15	4/21 (19%)	5
Pain	5/52 (9.6%)	6	3/21 (14.3%)	4
Pyrexia	15/52 (28.8%)	23	14/21 (66.7%)	25
Immune system disorders
Hypersensitivity	3/52 (5.8%)	4	0/21 (0%)	0
Infections and infestations
Cellulitis	3/52 (5.8%)	3	0/21 (0%)	0
Sinusitis	3/52 (5.8%)	3	2/21 (9.5%)	2
Upper respiratory tract infection	5/52 (9.6%)	7	3/21 (14.3%)	3
Urinary tract infection	4/52 (7.7%)	6	1/21 (4.8%)	1
Investigations
Alanine aminotransferase increased	12/52 (23.1%)	15	7/21 (33.3%)	17
Aspartate aminotransferase increased	14/52 (26.9%)	17	9/21 (42.9%)	19
Blood alkaline phosphatase increased	6/52 (11.5%)	6	5/21 (23.8%)	7
Haemoglobin decreased	4/52 (7.7%)	5	2/21 (9.5%)	7
Neutrophil count decreased	2/52 (3.8%)	2	4/21 (19%)	4
Weight decreased	3/52 (5.8%)	3	0/21 (0%)	0
White blood cell count decreased	0/52 (0%)	0	3/21 (14.3%)	5
Metabolism and nutrition disorders
Anorexia	10/52 (19.2%)	11	8/21 (38.1%)	12
Decreased appetite	2/52 (3.8%)	3	2/21 (9.5%)	2
Dehydration	1/52 (1.9%)	1	2/21 (9.5%)	2
Hyperglycaemia	11/52 (21.2%)	16	2/21 (9.5%)	10
Hypoalbuminaemia	1/52 (1.9%)	1	2/21 (9.5%)	4
Hypocalcaemia	2/52 (3.8%)	2	2/21 (9.5%)	6
Hypokalaemia	6/52 (11.5%)	9	6/21 (28.6%)	9
Hyponatraemia	4/52 (7.7%)	5	3/21 (14.3%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	9/52 (17.3%)	11	6/21 (28.6%)	13
Back pain	8/52 (15.4%)	8	5/21 (23.8%)	6
Bone pain	3/52 (5.8%)	4	3/21 (14.3%)	3
Muscle spasms	0/52 (0%)	0	2/21 (9.5%)	2
Musculoskeletal chest pain	6/52 (11.5%)	6	1/21 (4.8%)	2
Musculoskeletal pain	3/52 (5.8%)	5	4/21 (19%)	4
Myalgia	7/52 (13.5%)	14	5/21 (23.8%)	16
Pain in extremity	4/52 (7.7%)	5	6/21 (28.6%)	7
Nervous system disorders
Dizziness	3/52 (5.8%)	3	4/21 (19%)	5
Dysgeusia	5/52 (9.6%)	8	2/21 (9.5%)	2
Headache	11/52 (21.2%)	17	11/21 (52.4%)	12
Hypoaesthesia	3/52 (5.8%)	3	3/21 (14.3%)	3
Lethargy	2/52 (3.8%)	2	2/21 (9.5%)	3
Neuropathy peripheral	3/52 (5.8%)	3	3/21 (14.3%)	3
Paraesthesia	3/52 (5.8%)	3	3/21 (14.3%)	4
Sinus headache	0/52 (0%)	0	2/21 (9.5%)	2
Somnolence	0/52 (0%)	0	2/21 (9.5%)	2
Tremor	3/52 (5.8%)	3	0/21 (0%)	0
Psychiatric disorders
Anxiety	6/52 (11.5%)	6	3/21 (14.3%)	4
Confusional state	4/52 (7.7%)	5	0/21 (0%)	0
Insomnia	9/52 (17.3%)	9	3/21 (14.3%)	3
Renal and urinary disorders
Dysuria	3/52 (5.8%)	3	1/21 (4.8%)	1
Reproductive system and breast disorders
Breast pain	1/52 (1.9%)	1	2/21 (9.5%)	2
Respiratory, thoracic and mediastinal disorders
Cough	14/52 (26.9%)	15	7/21 (33.3%)	9
Dyspnoea	15/52 (28.8%)	20	6/21 (28.6%)	10
Dyspnoea exertional	5/52 (9.6%)	6	0/21 (0%)	0
Epistaxis	5/52 (9.6%)	5	2/21 (9.5%)	2
Hypoxia	3/52 (5.8%)	3	0/21 (0%)	0
Nasal congestion	3/52 (5.8%)	3	0/21 (0%)	0
Paranasal sinus hypersecretion	3/52 (5.8%)	5	4/21 (19%)	4
Pharyngolaryngeal pain	2/52 (3.8%)	2	5/21 (23.8%)	9
Sinus congestion	2/52 (3.8%)	2	2/21 (9.5%)	3
Skin and subcutaneous tissue disorders
Acne	0/52 (0%)	0	2/21 (9.5%)	5
Alopecia	8/52 (15.4%)	8	3/21 (14.3%)	3
Dry skin	5/52 (9.6%)	6	1/21 (4.8%)	1
Erythema	5/52 (9.6%)	6	4/21 (19%)	9
Night sweats	5/52 (9.6%)	5	3/21 (14.3%)	3
Pruritus	9/52 (17.3%)	10	4/21 (19%)	6
Rash	23/52 (44.2%)	30	15/21 (71.4%)	18
Rash macular	3/52 (5.8%)	4	1/21 (4.8%)	1
Vascular disorders
Flushing	1/52 (1.9%)	1	6/21 (28.6%)	6
Lymphoedema	6/52 (11.5%)	9	2/21 (9.5%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.