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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00113763
• Other study ID #: 20020408
• Status: Completed
• Phase: Phase 3
• Start date: January 1, 2004
• Est. completion date: June 1, 2009

Study information

• Verified date: November 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 463
• Est. completion date: June 1, 2009
• Est. primary completion date: October 1, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Metastases

Intervention

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).

Drug:
• Panitumumab
Intravenous infusion at a dose of 6 mg/kg once every 2 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival Time	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.	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.
Secondary	Overall Survival	Kaplan-Meier estimates of median time from randomization to death.	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.
Secondary	Objective Tumor Response	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.	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.
Secondary	Duration of Response	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).	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.
Secondary	Time to Response	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.	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.
Secondary	Time to Disease Progression	Kaplan-Meier estimates of median time from randomization to disease progression or death due to disease progression (whichever occurs first)	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.
Secondary	Time to Treatment Failure	Kaplan-Meier estimate of the median time from randomization to the date the decision was made to end treatment for any reason.	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.
Secondary	Duration of Stable Disease	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.	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.

External Links

•   AmgenTrials clinical trials website
•   FDA-approved Drug Labeling