Evaluating Panitumumab (ABX-EGF) Plus Best Supportive Care Versus Best Supportive Care in Patients With Metastatic Colorectal Cancer

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00113763
• Collaborator: (none)
• Enrollment: 463
• Arms: 2
• Duration (Months): 65

Study Details

Study Description

Brief Summary

The purpose of this study is to determine that panitumumab, using the proposed regimen, will safely increase progression free survival in patients with metastatic colorectal cancer who have failed available treatment options (i.e., patients who developed progressive disease or relapsed while on or after prior fluoropyrimidine, irinotecan and oxaliplatin chemotherapy).

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer; Metastases	Other: Best supportive care; Drug: Panitumumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 463 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomized, Phase 3 Clinical Trial of ABX-EGF Plus Best Supportive Care Versus Best Supportive Care in Subjects With Metastatic Colorectal Cancer
• Study Start Date: Jan 1, 2004
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panitumumab plus best supportive care Panitumumab will be administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants develop progressive disease or are unable to tolerate study drug. Participants will also receive best supportive care (BSC) as judged appropriate by the investigator and according to institutional guidelines.	Drug: Panitumumab; Intravenous infusion at a dose of 6 mg/kg once every 2 weeks.; Other Names: ABX-EGF
Other: Best Supportive Care Best supportive care will be defined in this study as the best care available as judged appropriate by the investigator and according to institutional guidelines and will include antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care will not include anti-neoplastic chemotherapy.	Other: Best supportive care; Best supportive care as site routine excluding: antineoplastic chemotherapy, investigational agents, anti-EGFr(Epidermal growth factor receptor) targeting agents other than ABX-EGF(Panitumumab), experimental or approved anti-tumor therapies (e.g. Avastin), chemotherapy, radiotherapy (with the exception of radiotherapy for pain control limited to bone metastases).

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival Time [From randomization to the data cut-off date of 30 June 2005. The median follow-up time was 20.0 weeks in the panitumumab plus BSC group and 18.2 weeks in the BSC alone group.]

   Kaplan-Meier estimates of median time from randomization to either death or first observed disease progression, whichever occurred first. Participants were evaluated for tumor response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) based on the response assessment from a blinded review of radiographic scans by the Independent Review Committee. Progressive disease defined as least a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the nadir SLD recorded since the treatment started or the appearance of one or more new lesions, or the unequivocal progression of existing non-target lesions.

Secondary Outcome Measures

1. Overall Survival [From randomization until the data cut-off date for overall survival of 15 March 2006. The median actual follow-up time was 30 weeks for the panitumumab plus BSC group and 31 weeks for the BSC alone group.]

   Kaplan-Meier estimates of median time from randomization to death.

2. Objective Tumor Response [From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.]

   Defined as the number of participants with a confirmed complete or partial tumor response, confirmed by a scan no less than 4 weeks after the criteria for response were first met. Participants were evaluated for tumor response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) based on the response assessment from a blinded review of radiographic scans by the Independent Review Committee. Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): disappearance of all target lesions, and persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease, or, at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD, with no progressive disease of non-target lesions.

3. Duration of Response [From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.]

   Kaplan-Meier estimate of the median time from first confirmed objective tumor response to first observed progression of disease or death due to progression of disease (whichever comes first).

4. Time to Response [From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.]

   Time to response was defined as the time from randomization to first partial or complete response, subsequently confirmed ≥ 4 weeks after the criteria for response were first met.

5. Time to Disease Progression [From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.]

   Kaplan-Meier estimates of median time from randomization to disease progression or death due to disease progression (whichever occurs first)

6. Time to Treatment Failure [From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.]

   Kaplan-Meier estimate of the median time from randomization to the date the decision was made to end treatment for any reason.

7. Duration of Stable Disease [From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.]

   Kaplan-Meier estimate of the median time from randomization to date of first observed progression of disease or death due to progression of disease (whichever comes first) for those participants with a best response of stable disease. Stable disease defined as neither sufficient shrinkage to qualify for a partial response nor sufficient increase to qualify for progressive disease taking as reference the nadir longest diameter since the treatment started, no unequivocal progression of existing non-target lesions, and no new lesions.

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

• Unidimensionally measurable disease

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

• At least 2 but not more than 3 prior chemotherapy regimens for colorectal cancer

• Adequate hematologic, renal and hepatic function

Exclusion Criteria:

• Symptomatic brain metastases requiring treatment

• History or evidence of interstitial pneumonitis or pulmonary fibrosis

• Use of systemic chemotherapy or radiotherapy within 30 days prior to enrollment

• Prior epidermal growth factor receptor (EGFr) targeting therapies

• Prior anti-tumor therapies including prior experimental agents or approved anti-tumor small molecules and biologics of short (less than a week) serum half life within 30 days before enrollment, or prior experimental or approved proteins within 3 months 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:

• AmgenTrials clinical trials website
• FDA-approved Drug Labeling

Publications

• Bai JP, Bell R, Buckman S, Burckart GJ, Eichler HG, Fang KC, Goodsaid FM, Jusko WJ, Lesko LL, Meibohm B, Patterson SD, Puig O, Smerage JB, Snider BJ, Wagner JA, Wang J, Walton MK, Weiner R. Translational biomarkers: from preclinical to clinical a report of 2009 AAPS/ACCP Biomarker Workshop. AAPS J. 2011 Jun;13(2):274-83. doi: 10.1208/s12248-011-9265-x. Epub 2011 Mar 30. Erratum in: AAPS J. 2011 Sep;13(3):493.
• Odom D, Barber B, Bennett L, Peeters M, Zhao Z, Kaye J, Wolf M, Wiezorek J. Health-related quality of life and colorectal cancer-specific symptoms in patients with chemotherapy-refractory metastatic disease treated with panitumumab. Int J Colorectal Dis. 2011 Feb;26(2):173-81. doi: 10.1007/s00384-010-1112-5. Epub 2010 Dec 29.
• Peeters M, Siena S, Van Cutsem E, Sobrero A, Hendlisz A, Cascinu S, Kalofonos H, Devercelli G, Wolf M, Amado RG. Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy. Cancer. 2009 Apr 1;115(7):1544-54. doi: 10.1002/cncr.24088.
• Siena S, Peeters M, Van Cutsem E, Humblet Y, Conte P, Bajetta E, Comandini D, Bodoky G, Van Hazel G, Salek T, Wolf M, Devercelli G, Woolley M, Amado RG. Association of progression-free survival with patient-reported outcomes and survival: results from a randomised phase 3 trial of panitumumab. Br J Cancer. 2007 Dec 3;97(11):1469-74. Epub 2007 Nov 27.
• Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M, Amado RG. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007 May 1;25(13):1658-64.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00113763
• Other Study ID Numbers: 20020408
• First Posted: Jun 13, 2005
• Last Update Posted: Aug 7, 2018
• Last Verified: Aug 1, 2015

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

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 16 January 2004 through 16 March 2005. Data are up until the data cutoff of 15 March 2007.

Arm/Group Title	Panitumumab Plus BSC	BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
Period Title: Overall Study
STARTED	231	232
Received Study Drug	229	0
COMPLETED	158	206
NOT COMPLETED	73	26

Baseline Characteristics

Arm/Group Title	Panitumumab Plus BSC	BSC Alone	Total
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.	Total of all reporting groups
Overall Participants	231	232	463
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.2 (10.3)	61.4 (10.8)	61.3 (10.5)
Sex: Female, Male (Count of Participants)
Female	85 36.8%	84 36.2%	169 36.5%
Male	146 63.2%	148 63.8%	294 63.5%
Race/Ethnicity, Customized (participants) [Number]
Japanese	0 0%	1 0.4%	1 0.2%
Aborigine	0 0%	0 0%	0 0%
Other	0 0%	0 0%	0 0%
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 0.9%	2 0.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 0.4%	0 0%	1 0.2%
White or Caucasian	229 99.1%	228 98.3%	457 98.7%
Hispanic or Latino	1 0.4%	1 0.4%	2 0.4%
Region of Enrollment (participants) [Number]
Central and Eastern Europe	20 8.7%	19 8.2%	39 8.4%
Western Europe	178 77.1%	180 77.6%	358 77.3%
Rest of World	33 14.3%	33 14.2%	66 14.3%
Eastern Cooperative Oncology Group (ECOG) performance status (participants) [Number]
0 or 1	200 86.6%	202 87.1%	402 86.8%
2	31 13.4%	30 12.9%	61 13.2%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival Time
Description	Kaplan-Meier estimates of median time from randomization to either death or first observed disease progression, whichever occurred first. Participants were evaluated for tumor response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) based on the response assessment from a blinded review of radiographic scans by the Independent Review Committee. Progressive disease defined as least a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the nadir SLD recorded since the treatment started or the appearance of one or more new lesions, or the unequivocal progression of existing non-target lesions.
Time Frame	From randomization to the data cut-off date of 30 June 2005. The median follow-up time was 20.0 weeks in the panitumumab plus BSC group and 18.2 weeks in the BSC alone group.

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT)

Arm/Group Title	Panitumumab Plus BSC	BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
Measure Participants	231	232
Median (95% Confidence Interval) [weeks]	8.0	7.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus BSC, BSC Alone
	Comments	Null hypothesis was no difference between treatment groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments	Stratified by baseline IVRS ECOG performance status and geographic region

2. Secondary Outcome

Title	Overall Survival
Description	Kaplan-Meier estimates of median time from randomization to death.
Time Frame	From randomization until the data cut-off date for overall survival of 15 March 2006. The median actual follow-up time was 30 weeks for the panitumumab plus BSC group and 31 weeks for the BSC alone group.

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT)

Arm/Group Title	Panitumumab Plus BSC	BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
Measure Participants	231	232
Median (95% Confidence Interval) [months]	6.4	6.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus BSC, BSC Alone
	Comments	Null hypothesis was no difference between treatment groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.806
	Comments	This analysis was conducted contingent on a statistically significant difference in the primary outcome, and adjusted to an a priori threshold for statistical significance at a 4% level for a multiple comparison involving objective tumor response
	Method	Log Rank
	Comments	Stratified by baseline IVRS ECOG performance status and geographic region

3. Secondary Outcome

Title	Objective Tumor Response
Description	Defined as the number of participants with a confirmed complete or partial tumor response, confirmed by a scan no less than 4 weeks after the criteria for response were first met. Participants were evaluated for tumor response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) based on the response assessment from a blinded review of radiographic scans by the Independent Review Committee. Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): disappearance of all target lesions, and persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease, or, at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD, with no progressive disease of non-target lesions.
Time Frame	From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT)

Arm/Group Title	Panitumumab Plus BSC	BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
Measure Participants	231	232
Number [participants]	22 9.5%	0 0%

4. Secondary Outcome

Title	Duration of Response
Description	Kaplan-Meier estimate of the median time from first confirmed objective tumor response to first observed progression of disease or death due to progression of disease (whichever comes first).
Time Frame	From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.

Outcome Measure Data

Analysis Population Description

Intention-to-treat participants who had a confirmed objective tumor response. No objective tumor responses were observed in the BSC alone treatment arm.

Arm/Group Title	Panitumumab Plus BSC	BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
Measure Participants	22	0
Median (95% Confidence Interval) [weeks]	18.4

5. Secondary Outcome

Title	Time to Response
Description	Time to response was defined as the time from randomization to first partial or complete response, subsequently confirmed ≥ 4 weeks after the criteria for response were first met.
Time Frame	From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) participants who had a confirmed objective tumor response. No objective tumor responses were observed in the BSC alone treatment arm.

Arm/Group Title	Panitumumab Plus BSC	BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
Measure Participants	22	0
Median (Inter-Quartile Range) [weeks]	7.9

6. Secondary Outcome

Title	Time to Disease Progression
Description	Kaplan-Meier estimates of median time from randomization to disease progression or death due to disease progression (whichever occurs first)
Time Frame	From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Panitumumab Plus BSC	BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
Measure Participants	231	232
Median (95% Confidence Interval) [weeks]	8.0	7.3

7. Secondary Outcome

Title	Time to Treatment Failure
Description	Kaplan-Meier estimate of the median time from randomization to the date the decision was made to end treatment for any reason.
Time Frame	From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT)

Arm/Group Title	Panitumumab Plus BSC	BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
Measure Participants	231	232
Median (95% Confidence Interval) [weeks]	9.0	7.1

8. Secondary Outcome

Title	Duration of Stable Disease
Description	Kaplan-Meier estimate of the median time from randomization to date of first observed progression of disease or death due to progression of disease (whichever comes first) for those participants with a best response of stable disease. Stable disease defined as neither sufficient shrinkage to qualify for a partial response nor sufficient increase to qualify for progressive disease taking as reference the nadir longest diameter since the treatment started, no unequivocal progression of existing non-target lesions, and no new lesions.
Time Frame	From randomization until the data cutoff of 15 March 2007. The median follow-up time was 29.6 weeks in the panitumumab plus BSC group and 31.8 weeks in the BSC alone group.

Outcome Measure Data

Analysis Population Description

Participants who had a best overall response of stable disease

Arm/Group Title	Panitumumab Plus BSC	BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
Measure Participants	61	24
Median (95% Confidence Interval) [weeks]	24.0	17.6

9. Post-Hoc Outcome

Title	Progression-free Survival Time (Wild-type KRAS)
Description	Kaplan-Meier estimates of median time from randomization to either death or first observed disease progression among participants with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) status. Participants were evaluated for tumor response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) based on the response assessment from a blinded review of radiographic scans by the Independent Review Committee. Progressive disease defined as least a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the nadir SLD recorded since the treatment started or the appearance of one or more new lesions, or the unequivocal progression of existing non-target lesions.
Time Frame	From randomization until the data cutoff of 15 March 2007. The median follow-up time in patients with wild-type KRAS was 36.8 weeks in the panitumumab plus BSC group and 35.7 weeks in the BSC alone group.

Outcome Measure Data

Analysis Population Description

Wild-type KRAS Efficacy Analysis Set, a subset of the Intention-to-Treat set with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) status.

Arm/Group Title	Panitumumab Plus Best Supportive Care	BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
Measure Participants	124	119
Median (95% Confidence Interval) [weeks]	12.3	7.3

10. Post-Hoc Outcome

Title	Progression-free Survival Time (Mutant KRAS)
Description	Kaplan-Meier estimates of median time from randomization to either death or first observed disease progression among participants with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) status. Participants were evaluated for tumor response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) based on the response assessment from a blinded review of radiographic scans by the Independent Review Committee. Progressive disease defined as least a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the nadir SLD recorded since the treatment started or the appearance of one or more new lesions, or the unequivocal progression of existing non-target lesions.
Time Frame	From randomization until the data cutoff of 15 March 2007. The median follow-up time in patients with mutant KRAS was 24.4 weeks in the panitumumab plus BSC group and 23.9 weeks in the BSC alone group.

Outcome Measure Data

Analysis Population Description

Mutant KRAS Efficacy Analysis Set, a subset of the Intention-to-Treat set with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) status.

Arm/Group Title	Panitumumab Plus Best Supportive Care	BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.	Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
Measure Participants	84	100
Median (95% Confidence Interval) [weeks]	7.4	7.3

Adverse Events

Time Frame	First dose through maximum of safety FU or 30 days after last dose
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Safety Analysis set includes all randomized patients, analyzed according to the treatment they actually received. Hence, 2 patients randomized to Panitumumab Plus BSC treatment group are analyzed in the BSC Alone group for safety.
Arm/Group Title	Panitumumab Plus BSC		BSC Alone
Arm/Group Description	Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.		Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.
All Cause Mortality
	Panitumumab Plus BSC		BSC Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Panitumumab Plus BSC		BSC Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	101/229 (44.1%)		62/234 (26.5%)
Blood and lymphatic system disorders
ANAEMIA	1/229 (0.4%)		1/234 (0.4%)
FEBRILE NEUTROPENIA	1/229 (0.4%)		0/234 (0%)
Cardiac disorders
ARRHYTHMIA SUPRAVENTRICULAR	0/229 (0%)		1/234 (0.4%)
CARDIO-RESPIRATORY ARREST	1/229 (0.4%)		0/234 (0%)
CARDIOMYOPATHY	1/229 (0.4%)		0/234 (0%)
PERICARDITIS	1/229 (0.4%)		0/234 (0%)
SUPRAVENTRICULAR TACHYCARDIA	1/229 (0.4%)		0/234 (0%)
TACHYCARDIA	1/229 (0.4%)		0/234 (0%)
Eye disorders
ENDOPHTHALMITIS	1/229 (0.4%)		0/234 (0%)
Gastrointestinal disorders
ABDOMINAL DISTENSION	1/229 (0.4%)		0/234 (0%)
ABDOMINAL PAIN	8/229 (3.5%)		8/234 (3.4%)
ABDOMINAL PAIN LOWER	1/229 (0.4%)		0/234 (0%)
ABDOMINAL PAIN UPPER	0/229 (0%)		1/234 (0.4%)
ASCITES	4/229 (1.7%)		2/234 (0.9%)
CONSTIPATION	7/229 (3.1%)		0/234 (0%)
DIARRHOEA	1/229 (0.4%)		0/234 (0%)
DUODENAL STENOSIS	0/229 (0%)		1/234 (0.4%)
GASTRIC ULCER	1/229 (0.4%)		0/234 (0%)
GASTRITIS	1/229 (0.4%)		0/234 (0%)
GASTROINTESTINAL HAEMORRHAGE	1/229 (0.4%)		0/234 (0%)
GASTROINTESTINAL OBSTRUCTION	2/229 (0.9%)		0/234 (0%)
INTESTINAL OBSTRUCTION	11/229 (4.8%)		4/234 (1.7%)
MELAENA	1/229 (0.4%)		0/234 (0%)
NAUSEA	1/229 (0.4%)		2/234 (0.9%)
PERITONITIS	1/229 (0.4%)		0/234 (0%)
PROCTALGIA	0/229 (0%)		1/234 (0.4%)
RECTAL DISCHARGE	0/229 (0%)		1/234 (0.4%)
RECTAL HAEMORRHAGE	2/229 (0.9%)		0/234 (0%)
SMALL INTESTINAL OBSTRUCTION	1/229 (0.4%)		1/234 (0.4%)
VOMITING	4/229 (1.7%)		5/234 (2.1%)
General disorders
ASTHENIA	4/229 (1.7%)		2/234 (0.9%)
CATHETER RELATED COMPLICATION	1/229 (0.4%)		0/234 (0%)
CHEST PAIN	1/229 (0.4%)		0/234 (0%)
FATIGUE	1/229 (0.4%)		1/234 (0.4%)
GENERAL PHYSICAL HEALTH DETERIORATION	14/229 (6.1%)		6/234 (2.6%)
HYPERTHERMIA	1/229 (0.4%)		0/234 (0%)
MUCOSAL INFLAMMATION	1/229 (0.4%)		0/234 (0%)
MULTI-ORGAN FAILURE	1/229 (0.4%)		0/234 (0%)
OEDEMA	1/229 (0.4%)		0/234 (0%)
OEDEMA PERIPHERAL	2/229 (0.9%)		0/234 (0%)
PELVIC MASS	1/229 (0.4%)		0/234 (0%)
PERFORMANCE STATUS DECREASED	1/229 (0.4%)		1/234 (0.4%)
PYREXIA	1/229 (0.4%)		8/234 (3.4%)
Hepatobiliary disorders
BILE DUCT STENOSIS	0/229 (0%)		1/234 (0.4%)
CHOLANGITIS	0/229 (0%)		2/234 (0.9%)
CHOLELITHIASIS	1/229 (0.4%)		0/234 (0%)
CHOLESTASIS	0/229 (0%)		1/234 (0.4%)
HEPATIC FAILURE	5/229 (2.2%)		4/234 (1.7%)
HEPATOMEGALY	2/229 (0.9%)		0/234 (0%)
HEPATORENAL FAILURE	1/229 (0.4%)		0/234 (0%)
HYPERBILIRUBINAEMIA	3/229 (1.3%)		2/234 (0.9%)
JAUNDICE	4/229 (1.7%)		3/234 (1.3%)
JAUNDICE CHOLESTATIC	1/229 (0.4%)		0/234 (0%)
LIVER DISORDER	1/229 (0.4%)		0/234 (0%)
Immune system disorders
HYPERSENSITIVITY	1/229 (0.4%)		0/234 (0%)
Infections and infestations
ABDOMINAL ABSCESS	0/229 (0%)		1/234 (0.4%)
BACTERIAL SEPSIS	0/229 (0%)		1/234 (0.4%)
CYSTITIS	1/229 (0.4%)		0/234 (0%)
DIARRHOEA INFECTIOUS	1/229 (0.4%)		0/234 (0%)
EPSTEIN-BARR VIRUS INFECTION	1/229 (0.4%)		0/234 (0%)
EYE INFECTION STAPHYLOCOCCAL	1/229 (0.4%)		0/234 (0%)
HAEMOPHILUS INFECTION	1/229 (0.4%)		0/234 (0%)
LOCALISED INFECTION	0/229 (0%)		1/234 (0.4%)
LUNG INFECTION	1/229 (0.4%)		0/234 (0%)
PARONYCHIA	1/229 (0.4%)		0/234 (0%)
SEPSIS	1/229 (0.4%)		1/234 (0.4%)
SEPTIC SHOCK	0/229 (0%)		2/234 (0.9%)
STAPHYLOCOCCAL SEPSIS	1/229 (0.4%)		0/234 (0%)
URINARY TRACT INFECTION	1/229 (0.4%)		0/234 (0%)
WOUND INFECTION	0/229 (0%)		1/234 (0.4%)
Injury, poisoning and procedural complications
FEMUR FRACTURE	1/229 (0.4%)		0/234 (0%)
INCISIONAL HERNIA	1/229 (0.4%)		0/234 (0%)
LUMBAR VERTEBRAL FRACTURE	0/229 (0%)		1/234 (0.4%)
OVERDOSE	1/229 (0.4%)		0/234 (0%)
TIBIA FRACTURE	1/229 (0.4%)		0/234 (0%)
Investigations
BLOOD BILIRUBIN INCREASED	1/229 (0.4%)		2/234 (0.9%)
BLOOD CREATININE INCREASED	0/229 (0%)		1/234 (0.4%)
Metabolism and nutrition disorders
ANOREXIA	3/229 (1.3%)		1/234 (0.4%)
CACHEXIA	2/229 (0.9%)		0/234 (0%)
DECREASED APPETITE	1/229 (0.4%)		0/234 (0%)
DEHYDRATION	4/229 (1.7%)		1/234 (0.4%)
DIABETES MELLITUS	1/229 (0.4%)		0/234 (0%)
FAILURE TO THRIVE	1/229 (0.4%)		0/234 (0%)
HYPOKALAEMIA	1/229 (0.4%)		0/234 (0%)
HYPOMAGNESAEMIA	1/229 (0.4%)		0/234 (0%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/229 (0.4%)		0/234 (0%)
BACK PAIN	3/229 (1.3%)		0/234 (0%)
BONE PAIN	1/229 (0.4%)		1/234 (0.4%)
MYALGIA	0/229 (0%)		1/234 (0.4%)
NECK PAIN	0/229 (0%)		2/234 (0.9%)
PAIN IN EXTREMITY	1/229 (0.4%)		0/234 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLADDER CANCER	1/229 (0.4%)		0/234 (0%)
CANCER PAIN	0/229 (0%)		1/234 (0.4%)
COLON CANCER	1/229 (0.4%)		0/234 (0%)
COLON CANCER METASTATIC	1/229 (0.4%)		2/234 (0.9%)
COLORECTAL CANCER	16/229 (7%)		9/234 (3.8%)
COLORECTAL CANCER METASTATIC	30/229 (13.1%)		24/234 (10.3%)
METASTASES TO CENTRAL NERVOUS SYSTEM	1/229 (0.4%)		1/234 (0.4%)
METASTASES TO LIVER	2/229 (0.9%)		0/234 (0%)
METASTASES TO LUNG	2/229 (0.9%)		0/234 (0%)
METASTASES TO PERITONEUM	0/229 (0%)		1/234 (0.4%)
METASTASES TO PLEURA	1/229 (0.4%)		0/234 (0%)
METASTASES TO SPINE	0/229 (0%)		1/234 (0.4%)
PERITONEAL CARCINOMA	1/229 (0.4%)		0/234 (0%)
RECTAL CANCER	0/229 (0%)		1/234 (0.4%)
TUMOUR HAEMORRHAGE	1/229 (0.4%)		0/234 (0%)
TUMOUR INVASION	1/229 (0.4%)		0/234 (0%)
TUMOUR NECROSIS	1/229 (0.4%)		1/234 (0.4%)
Nervous system disorders
CEREBROVASCULAR ACCIDENT	1/229 (0.4%)		0/234 (0%)
COMA	2/229 (0.9%)		0/234 (0%)
COMA HEPATIC	0/229 (0%)		1/234 (0.4%)
DEPRESSED LEVEL OF CONSCIOUSNESS	2/229 (0.9%)		0/234 (0%)
EPILEPSY	2/229 (0.9%)		0/234 (0%)
HEMIPARESIS	2/229 (0.9%)		1/234 (0.4%)
HEPATIC ENCEPHALOPATHY	2/229 (0.9%)		2/234 (0.9%)
LETHARGY	1/229 (0.4%)		0/234 (0%)
LOSS OF CONSCIOUSNESS	1/229 (0.4%)		0/234 (0%)
SOMNOLENCE	1/229 (0.4%)		0/234 (0%)
SPINAL CORD COMPRESSION	1/229 (0.4%)		1/234 (0.4%)
STUPOR	0/229 (0%)		1/234 (0.4%)
TRANSIENT ISCHAEMIC ATTACK	1/229 (0.4%)		0/234 (0%)
Psychiatric disorders
ALCOHOLISM	1/229 (0.4%)		0/234 (0%)
CONFUSIONAL STATE	0/229 (0%)		2/234 (0.9%)
DEPRESSION	1/229 (0.4%)		0/234 (0%)
Renal and urinary disorders
DYSURIA	1/229 (0.4%)		0/234 (0%)
HAEMATURIA	1/229 (0.4%)		0/234 (0%)
HYDRONEPHROSIS	1/229 (0.4%)		0/234 (0%)
NEPHROLITHIASIS	1/229 (0.4%)		0/234 (0%)
OLIGURIA	1/229 (0.4%)		0/234 (0%)
RENAL FAILURE	1/229 (0.4%)		0/234 (0%)
URETHRAL OBSTRUCTION	1/229 (0.4%)		0/234 (0%)
Reproductive system and breast disorders
FEMALE GENITAL TRACT FISTULA	0/229 (0%)		1/234 (0.4%)
PELVIC PAIN	1/229 (0.4%)		1/234 (0.4%)
PERINEAL PAIN	0/229 (0%)		1/234 (0.4%)
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE	1/229 (0.4%)		0/234 (0%)
DYSPNOEA	6/229 (2.6%)		4/234 (1.7%)
HAEMOPTYSIS	1/229 (0.4%)		0/234 (0%)
PLEURAL EFFUSION	1/229 (0.4%)		0/234 (0%)
PLEURISY	1/229 (0.4%)		0/234 (0%)
PULMONARY EMBOLISM	3/229 (1.3%)		0/234 (0%)
RESPIRATORY FAILURE	1/229 (0.4%)		0/234 (0%)
Skin and subcutaneous tissue disorders
DERMATITIS ALLERGIC	1/229 (0.4%)		0/234 (0%)
Vascular disorders
AXILLARY VEIN THROMBOSIS	1/229 (0.4%)		0/234 (0%)
DEEP VEIN THROMBOSIS	3/229 (1.3%)		0/234 (0%)
HAEMORRHAGE	1/229 (0.4%)		0/234 (0%)
JUGULAR VEIN THROMBOSIS	2/229 (0.9%)		0/234 (0%)
Other (Not Including Serious) Adverse Events
	Panitumumab Plus BSC		BSC Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	224/229 (97.8%)		171/234 (73.1%)
Blood and lymphatic system disorders
ANAEMIA	12/229 (5.2%)		6/234 (2.6%)
Eye disorders
GROWTH OF EYELASHES	13/229 (5.7%)		0/234 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	56/229 (24.5%)		36/234 (15.4%)
ABDOMINAL PAIN UPPER	19/229 (8.3%)		16/234 (6.8%)
CONSTIPATION	43/229 (18.8%)		21/234 (9%)
DIARRHOEA	48/229 (21%)		26/234 (11.1%)
NAUSEA	51/229 (22.3%)		35/234 (15%)
STOMATITIS	15/229 (6.6%)		2/234 (0.9%)
VOMITING	41/229 (17.9%)		27/234 (11.5%)
General disorders
ASTHENIA	28/229 (12.2%)		25/234 (10.7%)
FATIGUE	59/229 (25.8%)		34/234 (14.5%)
GENERAL PHYSICAL HEALTH DETERIORATION	13/229 (5.7%)		3/234 (1.3%)
MUCOSAL INFLAMMATION	14/229 (6.1%)		2/234 (0.9%)
OEDEMA PERIPHERAL	27/229 (11.8%)		13/234 (5.6%)
PYREXIA	37/229 (16.2%)		24/234 (10.3%)
Hepatobiliary disorders
HEPATOMEGALY	12/229 (5.2%)		8/234 (3.4%)
JAUNDICE	13/229 (5.7%)		7/234 (3%)
Infections and infestations
PARONYCHIA	57/229 (24.9%)		0/234 (0%)
Investigations
WEIGHT DECREASED	12/229 (5.2%)		3/234 (1.3%)
Metabolism and nutrition disorders
ANOREXIA	63/229 (27.5%)		44/234 (18.8%)
Musculoskeletal and connective tissue disorders
BACK PAIN	24/229 (10.5%)		16/234 (6.8%)
Psychiatric disorders
ANXIETY	14/229 (6.1%)		7/234 (3%)
INSOMNIA	15/229 (6.6%)		14/234 (6%)
Respiratory, thoracic and mediastinal disorders
COUGH	34/229 (14.8%)		17/234 (7.3%)
DYSPNOEA	36/229 (15.7%)		28/234 (12%)
Skin and subcutaneous tissue disorders
ACNE	31/229 (13.5%)		0/234 (0%)
DERMATITIS ACNEIFORM	131/229 (57.2%)		2/234 (0.9%)
DRY SKIN	23/229 (10%)		0/234 (0%)
ERYTHEMA	150/229 (65.5%)		2/234 (0.9%)
EXFOLIATIVE RASH	41/229 (17.9%)		0/234 (0%)
NAIL DISORDER	22/229 (9.6%)		0/234 (0%)
PRURITUS	132/229 (57.6%)		4/234 (1.7%)
RASH	51/229 (22.3%)		2/234 (0.9%)
SKIN EXFOLIATION	21/229 (9.2%)		0/234 (0%)
SKIN FISSURES	45/229 (19.7%)		1/234 (0.4%)
SKIN ULCER	13/229 (5.7%)		0/234 (0%)

Limitations/Caveats

[Not Specified]

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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.