Evaluating Panitumumab (ABX-EGF) Monotherapy in Patients With Metastatic Colorectal Cancer Following Treatment With Fluoropyrimidine, Irinotecan, and Oxaliplatin Chemotherapy

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00083616
• Collaborator: (none)
• Enrollment: 185
• Arm: 1
• Duration (Months): 57

Study Details

Study Description

Brief Summary

The purpose of this study is to determine that panitumumab will have clinically meaningful anti-tumor activity in patients with metastatic colorectal cancer who have developed progressive disease or relapsed while on or after prior fluoropyrimidine, irinotecan and oxaliplatin chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer; Metastatic Cancer	Biological: Panitumumab	Phase 2

Detailed Description

Panitumumab was administered once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons (eg, administrative decision). Participants then attended a safety follow-up visit 4 weeks from the last panitumumab infusion. Participants were subsequently contacted every 3 months from the last panitumumab infusion through month 24 to assess disease status and survival.

Study Design

• Study Type: Interventional
• Actual Enrollment: 185 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Multicenter Single Arm Clinical Trial of ABX-EGF Monotherapy in Subjects With Metastatic Colorectal Cancer Following Treatment With Fluoropyrimidine, Irinotecan, and Oxaliplatin Chemotherapy
• Study Start Date: Mar 1, 2004
• Actual Primary Completion Date: May 1, 2007
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panitumumab Participants received panitumumab 6 mg/kg once every 2 weeks weeks administered by intravenous (IV) infusion until progressive disease, inability to tolerate the investigational product, or discontinuation of treatment for other reasons.	Biological: Panitumumab; Panitumumab 6 mg/kg every once 2 weeks weeks administered by intravenous (IV) infusion.; Other Names: ABX-EGF Vectibix

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Objective Tumor Response Through Week 16 [16 weeks]

   Confirmed objective tumor response (complete or partial response) based on modified World Health Organization (WHO) criteria, through week 16. Tumor response was assessed by a central Independent Review Committee (IRC) and confirmation 4 weeks after initial assessment was required. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no "unequivocal progression" of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.

2. Duration of Response [Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.]

   The time from first objective response to first observed progression of disease or death if the death was due to disease progression (whichever comes first); participants who respond and have not progressed while on study or died for reasons other than disease progression while on study were censored at their last evaluable disease assessment date. Response (complete or partial response) was assessed per modified WHO criteria by the central IRC. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no "unequivocal progression" of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.

Secondary Outcome Measures

1. Number of Participants With Objective Tumor Response Throughout Study [Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.]

   Confirmed objective tumor response (complete or partial response) based on modified World Health Organization (WHO) criteria, throughout the duration of the study Tumor response was assessed by a central Independent Review Committee (IRC) and confirmation 4 weeks after initial assessment was required. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no "unequivocal progression" of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.

2. Time to Response [Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.]

   Median time from enrollment to objective tumor response for participants who responded.

3. Progression-free Survival Time [Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.]

   Kaplan-Meier estimate of median time from enrollment to death or first observed disease progression (whichever comes first). Participants who did not progress while on study and did not die while on study were censored at the last evaluable disease assessment date.

4. Time to Disease Progression [Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.]

   Kaplan-Meier estimate of the median time from enrollment to first observed disease progression or death if death was due to disease progression (whichever comes first). Participants who did not progress while on study or died for reasons other than disease progression while on study were censored at their last evaluable disease assessment date.

5. Time to Treatment Failure [Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.]

   Kaplan-Meier estimate of median time from enrollment to treatment failure, defined as the date the decision was made to end treatment. Participants remaining in the treatment phase at the time of the analysis were censored on their last visit date.

6. Duration of Stable Disease [Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.]

   Kaplan-Meier estimates of the median time from enrollment to the date of first observed disease progression or death due to disease progression among those participants with a best outcome of stable disease. Stable disease (SD): Neither sufficient shrinkage of Index lesions to qualify for partial response nor sufficient increase to qualify for progressive disease (PD) taking as reference the nadir sum of the products of the longest diameters (SPD) since the treatment started and the disappearance of or persistence of one or more non-index lesions not qualifying for PD.

7. Overall Survival [Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.]

   Kaplan-Meier estimate of median time from enrollment to death from any cause. Deaths were recorded during treatment, safety follow-up and long term follow-up.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Pathologic diagnosis of colorectal adenocarcinoma (diagnostic tissue obtained by tissue biopsy)

• Metastatic colorectal carcinoma

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

• Documented evidence of disease progression during, or following treatment, with fluoropyrimidine, irinotecan and oxaliplatin chemotherapy for metastatic colorectal cancer

• Radiographic documentation of disease progression during or within 6 months following the most recent chemotherapy regimen is required

• Bidimensionally measurable disease

• Tumor expressing epidermal growth factor receptor (EGFr) by immunohistochemistry

• At least 2 but no more than 3 prior chemotherapy regimens for metastatic colorectal cancer

• Adequate hematologic, renal and hepatic function

Exclusion Criteria:

• Symptomatic brain metastases requiring treatment

• Patient with a history of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis

• Use of systemic chemotherapy or radiotherapy within 30 days before enrollment

• Prior epidermal growth factor receptor targeting agents

• Prior anti-tumor therapies including prior experimental agents or approved anti-tumor small molecules and biologics of short (less than 1 week) serum half-life within 30 days before enrollment, or prior experimental or approved proteins with longer serum half-life (e.g., AvastinTM) within 6 weeks before enrollment

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• FDA-approved Drug Labeling
• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00083616
• Other Study ID Numbers: 20030167; NCT00087243
• First Posted: May 28, 2004
• Last Update Posted: Jan 10, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by Amgen: EGFr; Clinical Trial; Panitumumab; ABX-EGF; Immunex; Metastatic Cancer; Vectibix; Abgenix; Amgen
• Additional relevant MeSH terms: Colorectal Neoplasms; Neoplasm Metastasis; Panitumumab

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 1 March 2004 through 19 Jul 2006. Patient disposition is reported up until the data cut-off date of 22 December 2006. Completed study is defined as participants who either died on study or completed the safety follow-up visit (30 days after the last dose of panitumumab).

Arm/Group Title	Panitumumab (ABX-EGF)
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Period Title: Overall Study
STARTED	185
Received Study Medication	182
COMPLETED	154
NOT COMPLETED	31

Baseline Characteristics

Arm/Group Title	Panitumumab
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Overall Participants	185
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.6 (10.6)
Sex: Female, Male (Count of Participants)
Female	85 45.9%
Male	100 54.1%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaska Native	0 0%
Asian	4 2.2%
Black or African American	15 8.1%
Hispanic or Latino	19 10.3%
Japanese	0 0%
Native Hawaiian or Other Pacific Islander	1 0.5%
White or Caucasian	144 77.8%
Other	2 1.1%
Aborigine	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Objective Tumor Response Through Week 16
Description	Confirmed objective tumor response (complete or partial response) based on modified World Health Organization (WHO) criteria, through week 16. Tumor response was assessed by a central Independent Review Committee (IRC) and confirmation 4 weeks after initial assessment was required. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no "unequivocal progression" of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Measure Participants	142
Number [Participants]	5 2.7%

2. Primary Outcome

Title	Duration of Response
Description	The time from first objective response to first observed progression of disease or death if the death was due to disease progression (whichever comes first); participants who respond and have not progressed while on study or died for reasons other than disease progression while on study were censored at their last evaluable disease assessment date. Response (complete or partial response) was assessed per modified WHO criteria by the central IRC. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no "unequivocal progression" of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.

Outcome Measure Data

Analysis Population Description

Subset of the Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC), who had a confirmed obective tumor response

Arm/Group Title	Panitumumab
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Measure Participants	5
Median (95% Confidence Interval) [Weeks]	14.0

3. Secondary Outcome

Title	Number of Participants With Objective Tumor Response Throughout Study
Description	Confirmed objective tumor response (complete or partial response) based on modified World Health Organization (WHO) criteria, throughout the duration of the study Tumor response was assessed by a central Independent Review Committee (IRC) and confirmation 4 weeks after initial assessment was required. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no "unequivocal progression" of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Measure Participants	142
Number [Participants]	5 2.7%

4. Secondary Outcome

Title	Time to Response
Description	Median time from enrollment to objective tumor response for participants who responded.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.

Outcome Measure Data

Analysis Population Description

Subset of Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC), who had a confirmed objective tumor response

Arm/Group Title	Panitumumab
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Measure Participants	5
Median (Inter-Quartile Range) [Weeks]	11.0

5. Secondary Outcome

Title	Progression-free Survival Time
Description	Kaplan-Meier estimate of median time from enrollment to death or first observed disease progression (whichever comes first). Participants who did not progress while on study and did not die while on study were censored at the last evaluable disease assessment date.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Measure Participants	142
Median (95% Confidence Interval) [Weeks]	7.3

6. Secondary Outcome

Title	Time to Disease Progression
Description	Kaplan-Meier estimate of the median time from enrollment to first observed disease progression or death if death was due to disease progression (whichever comes first). Participants who did not progress while on study or died for reasons other than disease progression while on study were censored at their last evaluable disease assessment date.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Measure Participants	142
Median (95% Confidence Interval) [Weeks]	7.3

7. Secondary Outcome

Title	Time to Treatment Failure
Description	Kaplan-Meier estimate of median time from enrollment to treatment failure, defined as the date the decision was made to end treatment. Participants remaining in the treatment phase at the time of the analysis were censored on their last visit date.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Measure Participants	142
Median (95% Confidence Interval) [Weeks]	8.0

8. Secondary Outcome

Title	Duration of Stable Disease
Description	Kaplan-Meier estimates of the median time from enrollment to the date of first observed disease progression or death due to disease progression among those participants with a best outcome of stable disease. Stable disease (SD): Neither sufficient shrinkage of Index lesions to qualify for partial response nor sufficient increase to qualify for progressive disease (PD) taking as reference the nadir sum of the products of the longest diameters (SPD) since the treatment started and the disappearance of or persistence of one or more non-index lesions not qualifying for PD.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.

Outcome Measure Data

Analysis Population Description

Subset of Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC), with a best outcome of stable disease

Arm/Group Title	Panitumumab
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Measure Participants	31
Median (95% Confidence Interval) [Weeks]	23.9

9. Secondary Outcome

Title	Overall Survival
Description	Kaplan-Meier estimate of median time from enrollment to death from any cause. Deaths were recorded during treatment, safety follow-up and long term follow-up.
Time Frame	Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.

Outcome Measure Data

Analysis Population Description

Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)

Arm/Group Title	Panitumumab
Arm/Group Description	Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons.
Measure Participants	142
Median (95% Confidence Interval) [months]	7.0

Adverse Events

Time Frame	From the first dose through maximum of safety follow-up or 30 days after last dose; maximum time on study treatment was 1.25 years.
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Arm/Group Title	Panitumumab
Arm/Group Description
All Cause Mortality
	Panitumumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Panitumumab
	Affected / at Risk (%)	# Events
Total	62/182 (34.1%)
Blood and lymphatic system disorders
Anaemia	1/182 (0.5%)
Cardiac disorders
Atrial fibrillation	1/182 (0.5%)
Cardiac failure congestive	1/182 (0.5%)
Gastrointestinal disorders
Abdominal distension	3/182 (1.6%)
Abdominal hernia	1/182 (0.5%)
Abdominal pain	4/182 (2.2%)
Abdominal pain lower	1/182 (0.5%)
Ascites	3/182 (1.6%)
Colonic fistula	1/182 (0.5%)
Constipation	1/182 (0.5%)
Diarrhoea	1/182 (0.5%)
Duodenal obstruction	1/182 (0.5%)
Gastrointestinal haemorrhage	1/182 (0.5%)
Intestinal obstruction	2/182 (1.1%)
Nausea	2/182 (1.1%)
Pancreatitis	1/182 (0.5%)
Pancreatitis acute	1/182 (0.5%)
Reflux oesophagitis	1/182 (0.5%)
Small intestinal obstruction	6/182 (3.3%)
Vomiting	2/182 (1.1%)
General disorders
Early satiety	1/182 (0.5%)
Fatigue	1/182 (0.5%)
Pain	1/182 (0.5%)
Hepatobiliary disorders
Bile duct obstruction	2/182 (1.1%)
Cholangitis	1/182 (0.5%)
Hepatic function abnormal	1/182 (0.5%)
Hyperbilirubinaemia	1/182 (0.5%)
Jaundice cholestatic	1/182 (0.5%)
Immune system disorders
Hypersensitivity	1/182 (0.5%)
Infections and infestations
Bacteraemia	1/182 (0.5%)
Catheter related infection	1/182 (0.5%)
Cellulitis	1/182 (0.5%)
Endocarditis staphylococcal	1/182 (0.5%)
Folliculitis	1/182 (0.5%)
Lobar pneumonia	1/182 (0.5%)
Pneumonia	3/182 (1.6%)
Pneumonia bacterial	1/182 (0.5%)
Pyelonephritis	1/182 (0.5%)
Septic embolus	1/182 (0.5%)
Septic shock	1/182 (0.5%)
Urosepsis	1/182 (0.5%)
Injury, poisoning and procedural complications
Humerus fracture	1/182 (0.5%)
Lumbar vertebral fracture	1/182 (0.5%)
Investigations
Weight decreased	1/182 (0.5%)
Metabolism and nutrition disorders
Cachexia	1/182 (0.5%)
Dehydration	2/182 (1.1%)
Diabetes mellitus inadequate control	1/182 (0.5%)
Fluid retention	1/182 (0.5%)
Hyperkalaemia	1/182 (0.5%)
Hypocalcaemia	1/182 (0.5%)
Hypokalaemia	2/182 (1.1%)
Hypomagnesaemia	1/182 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	6/182 (3.3%)
Colon cancer metastatic	6/182 (3.3%)
Colorectal cancer	5/182 (2.7%)
Metastases to central nervous system	1/182 (0.5%)
Neoplasm progression	1/182 (0.5%)
Rectal cancer metastatic	2/182 (1.1%)
Nervous system disorders
Anoxic encephalopathy	1/182 (0.5%)
Convulsion	2/182 (1.1%)
Dizziness	1/182 (0.5%)
Hepatic encephalopathy	1/182 (0.5%)
Speech disorder	1/182 (0.5%)
Spinal cord compression	1/182 (0.5%)
Vocal cord paralysis	1/182 (0.5%)
Psychiatric disorders
Anxiety	2/182 (1.1%)
Confusional state	1/182 (0.5%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/182 (0.5%)
Bronchial obstruction	1/182 (0.5%)
Dyspnoea	7/182 (3.8%)
Hypoxia	2/182 (1.1%)
Pleural effusion	3/182 (1.6%)
Pneumothorax	1/182 (0.5%)
Pulmonary embolism	1/182 (0.5%)
Pulmonary oedema	1/182 (0.5%)
Respiratory arrest	1/182 (0.5%)
Respiratory distress	1/182 (0.5%)
Respiratory failure	4/182 (2.2%)
Vascular disorders
Circulatory collapse	1/182 (0.5%)
Deep vein thrombosis	3/182 (1.6%)
Hypotension	1/182 (0.5%)
Other (Not Including Serious) Adverse Events
	Panitumumab
	Affected / at Risk (%)	# Events
Total	176/182 (96.7%)
Gastrointestinal disorders
Abdominal pain	34/182 (18.7%)
Ascites	11/182 (6%)
Constipation	36/182 (19.8%)
Diarrhoea	48/182 (26.4%)
Dyspepsia	12/182 (6.6%)
Nausea	58/182 (31.9%)
Stomatitis	16/182 (8.8%)
Vomiting	38/182 (20.9%)
General disorders
Asthenia	12/182 (6.6%)
Chills	11/182 (6%)
Fatigue	66/182 (36.3%)
Oedema peripheral	17/182 (9.3%)
Pyrexia	23/182 (12.6%)
Infections and infestations
Paronychia	32/182 (17.6%)
Rash pustular	16/182 (8.8%)
Urinary tract infection	13/182 (7.1%)
Investigations
Weight decreased	19/182 (10.4%)
Metabolism and nutrition disorders
Anorexia	31/182 (17%)
Decreased appetite	11/182 (6%)
Dehydration	12/182 (6.6%)
Hypokalaemia	15/182 (8.2%)
Hypomagnesaemia	20/182 (11%)
Musculoskeletal and connective tissue disorders
Back pain	21/182 (11.5%)
Pain in extremity	10/182 (5.5%)
Nervous system disorders
Dizziness	12/182 (6.6%)
Headache	18/182 (9.9%)
Psychiatric disorders
Anxiety	14/182 (7.7%)
Depression	10/182 (5.5%)
Insomnia	16/182 (8.8%)
Respiratory, thoracic and mediastinal disorders
Cough	24/182 (13.2%)
Dyspnoea	29/182 (15.9%)
Skin and subcutaneous tissue disorders
Acne	10/182 (5.5%)
Dermatitis acneiform	125/182 (68.7%)
Dry skin	28/182 (15.4%)
Erythema	112/182 (61.5%)
Exfoliative rash	30/182 (16.5%)
Nail disorder	15/182 (8.2%)
Pruritus	96/182 (52.7%)
Rash	44/182 (24.2%)
Rash papular	12/182 (6.6%)
Skin exfoliation	17/182 (9.3%)
Skin fissures	24/182 (13.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.