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

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
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 :	January 2004
Actual Primary Completion Date :	October 2008
Actual Study Completion Date :	June 2009

Arms and Interventions

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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 Name: ABX-EGF
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

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Primary Outcome Measures :

1. Progression-free Survival Time [ 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. ]
   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 [ 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. ]
   Kaplan-Meier estimates of median time from randomization to death.
2. Objective Tumor Response [ 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. ]
   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 [ 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. ]
   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 [ 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. ]
   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 [ 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. ]
   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 [ 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. ]
   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 [ 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. ]
   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

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Sponsors and Collaborators

Amgen

Investigators

Study Director:	MD	Amgen

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Boeckx N, Koukakis R, Op de Beeck K, Rolfo C, Van Camp G, Siena S, Tabernero J, Douillard JY, André T, Peeters M. Effect of Primary Tumor Location on Second- or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies. Clin Colorectal Cancer. 2018 Mar 8. pii: S1533-0028(17)30493-0. doi: 10.1016/j.clcc.2018.03.005. [Epub ahead of print]

Peeters M, Kafatos G, Taylor A, Gastanaga VM, Oliner KS, Hechmati G, Terwey JH, van Krieken JH. Prevalence of RAS mutations and individual variation patterns among patients with metastatic colorectal cancer: A pooled analysis of randomised controlled trials. Eur J Cancer. 2015 Sep;51(13):1704-13. doi: 10.1016/j.ejca.2015.05.017. Epub 2015 Jun 3.

Poulin-Costello M, Azoulay L, Van Cutsem E, Peeters M, Siena S, Wolf M. An analysis of the treatment effect of panitumumab on overall survival from a phase 3, randomized, controlled, multicenter trial (20020408) in patients with chemotherapy refractory metastatic colorectal cancer. Target Oncol. 2013 Jun;8(2):127-36. doi: 10.1007/s11523-013-0271-z. Epub 2013 Apr 27.

Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008 Apr 1;26(10):1626-34. doi: 10.1200/JCO.2007.14.7116. Epub 2008 Mar 3.

Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT00113763 History of Changes
Other Study ID Numbers:	20020408
First Posted:	June 13, 2005
Results First Posted:	January 3, 2014
Last Update Posted:	July 23, 2014
Last Verified:	July 2014

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; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases	Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs