Panitumumab and Bortezomib for Patients With Advanced Colorectal Cancer
This study is for patients with colon cancer that cannot be fully removed by surgery and has come back after or not responded to standard chemotherapy treatment.
Subjects will be enrolled to either the first part of the study (Phase I) or the second part of the study (Phase II). Phase I will be completed before Phase II will start. The purpose of the Phase I part is to find the highest dose of bortezomib that can be given with panitumumab without causing severe side effects. The purpose of the Phase II part is to test the effects the two drugs have on subjects with colorectal cancer.
Panitumumab is a drug that targets a protein important for the growth of cancer cells known as EGFR. By blocking the activity of the protein, panitumumab can block cancer cell growth and even lead to their death. Panitumumab is given intravenously once every two weeks. Panitumumab is approved by the FDA for patients with colorectal cancer.
Bortezomib is a drug that targets a part of the cancer cell known as the proteosome. By inhibiting the proteosome, bortezomib can inhibit cancer cell growth and even lead to their death. Bortezomib is given intravenously, once a week, 3 out of every 4 weeks. Bortezomib is not FDA approved for the treatment of colorectal cancer.
As part of this study the investigators will be taking biopsies of patients' tumors before any treatment, after starting with the panitumumab alone, and after receiving both the panitumumab and bortezomib. The investigators want to investigate what markers inside tumors may relate to how well these two medications work. These biopsies are required as part of the study.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Clinical Trial of the Anti-EGFR Monoclonal Antibody, Panitumumab, and the Proteosomal Inhibitor, Bortezomib, in Patients With Advanced, Refractory KRAS Wild-Type Colorectal Cancer|
- Maximum tolerated dose [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]The maximum tolerated dose of bortezomib to be used in combination with panitumumab
- Disease control rate [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]Stable disease after 2 cycles, partial response or complete response
- Overall response rate [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]Partial response plus complete response
- Overall survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]Time from study registration to death
- Duration of disease control [ Time Frame: 2 years ] [ Designated as safety issue: No ]Time from study registration until progressive disease
- Pharmacodynamic effects [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]pharmacodynamic effects of panitumumab alone and in combination with bortezomib on the EGFR and proteosome pathways by phosphoprotein pathway analysis
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Combination of Panitumumab and Bortezomib
IV panitumumab and bortezomib
Drug: Panitumumab and bortezomib
Panitumumab 6 mg/kg IV over 60 minutes on Day -14 (first cycle only), then Day 1 and 15 of each 28-day cycle.
Bortezomib will be administered in escalating doses until the maximum tolerated dose is determined and then at the maximum tolerated dose as an IV bolus injection over 3-5 seconds on Day 1, 8, and 15 of each 28-day cycle.
|Contact: Karen Vogel, RNemail@example.com|
|Contact: Lisa Ley, RN BSNfirstname.lastname@example.org|
|United States, District of Columbia|
|Georgetown Lombardi Comprehensive Cancer Center||Recruiting|
|Washington, District of Columbia, United States, 20007|
|Contact: Karen Vogel, RN 202-687-6974 email@example.com|
|Contact: Lisa Ley, RN MSN 202-687-6653 Leyl@georgetown.edu|
|Principal Investigator: Michael Pishvaian, MD PhD|
|Principal Investigator:||Michael Pishvaian, MD PhD||Georgetown University|